近年来，关于麸质（gluten）饮食的讨论日益增多，从医学界对乳糜泻（Celiac Disease, CD）患者严格无麸质饮食的强调，到普通大众对“无麸质”标签的追捧，麸质饮食已成为一个备受关注且充满争议的话题。这种争议不仅限于科学和医学领域，还广泛渗透到社会认知、商业市场乃至个人生活方式的选择中。一方面，对于乳糜泻患者而言，麸质是引发自身免疫反应、导致肠道损伤的明确诱因，严格无麸质饮食是唯一有效的治疗手段 1；另一方面，大量健康人群却也主动选择规避麸质，认为无麸质饮食能带来健康益处，甚至将其视为一种时尚生活方式，尽管缺乏充分的科学证据支持。
本综述旨在对麸质饮食的争议进行多维度剖析。我们将首先从麸质的生物学基础及其在人类饮食中的历史角色入手，揭示其作为一种常见膳食成分的本质。随后，本文将深入探讨争议的核心——麸质对健康影响的科学分歧，重点阐述乳糜泻的病理机制、无麸质饮食的必要性，并审视非乳糜泻麸质敏感性（Non-Celiac Gluten Sensitivity, NCGS）的证据强度与诊断困境，同时探讨健康人群限制麸质的潜在营养风险。紧接着，我们将分析社会认知和商业市场在推波助澜这一争议中的作用，包括媒体传播的偏差以及无麸质食品市场的迅速扩张及其监管挑战。最后，本综述将总结当前学界关于麸质饮食的基本共识，并展望未来需要解决的关键研究方向，以期为理解麸质饮食争议提供一个全面、深入且基于证据的视角。
1. 麸质的生物学基础与传统饮食角色
1.1 麸质的化学组成与食物分布特征
麸质（Gluten）是小麦、大麦、黑麦等谷物中主要储存蛋白的复合混合物，赋予面团独特的粘弹特性，对烘焙食品的质地和结构至关重要 23。虽然“麸质”一词常用于泛指，但其严格意义上的化学构成主要包括两大类蛋白质：醇溶谷蛋白（gliadins）和谷蛋白（glutenins） 45。这两类蛋白在水中不溶，但在面粉与水混合形成面团时，它们能够相互作用并形成一个连续的、具有粘弹性的蛋白质网络 36。
醇溶谷蛋白是单体蛋白质，根据其初级结构可分为α/β-、γ-和ω-型，分子量通常在28,000至55,000道尔顿之间 5。它们主要负责面团的粘性，其中一些肽段对胃肠道消化具有高度抵抗性，可能在麸质相关疾病中扮演关键角色 7。谷蛋白则是由通过二硫键连接在一起的聚合蛋白质构成，分子量范围广泛，可从约500,000道尔顿延伸至超过1000万道尔顿 5。根据分子量大小，谷蛋白又分为高分子量谷蛋白亚基（HMW-GS，分子量67,000-88,000）和低分子量谷蛋白亚基（LMW-GS，分子量32,000-35,000） 5。高分子量谷蛋白亚基尤其对决定面团弹性起关键作用，是麸质弹性骨架的重要组成部分 23。麸质蛋白中富含谷氨酰胺和脯氨酸，这些氨基酸的独特序列使其能形成广泛的链间氢键，进一步增强了其弹性和结构稳定性 58。
除了小麦，麸质及其类似储存蛋白也存在于其他禾本科谷物中，例如黑麦中的黑麦醇溶蛋白（secalin）、大麦中的大麦醇溶蛋白（hordein）以及燕麦中的燕麦醇溶蛋白（avenins） 4。尽管燕麦中天然存在的燕麦醇溶蛋白通常不会引发乳糜泻患者的免疫反应，但由于其在加工和储存过程中可能与小麦、大麦或黑麦发生交叉污染，因此市售的燕麦产品也可能含有麸质 4。
常见的含麸质食品类别广泛，几乎涵盖了所有以小麦、大麦或黑麦为主要原料的加工食品，包括但不限于：
- 谷物制品：面包、面条、饼干、蛋糕、披萨、谷物早餐、麦片、馒头、包子等。
- 烘焙食品：各种糕点、酥皮点心、油条。
- 啤酒和麦芽饮料：大麦是啤酒酿造的主要原料之一，因此绝大多数啤酒都含有麸质。
- 加工食品添加剂：麸质常被用作增稠剂、稳定剂、乳化剂或风味增强剂，存在于许多加工肉制品（如香肠、午餐肉）、调味品（如酱油、沙拉酱）、汤料、糖果和药品中 4。
鉴于麸质在食品工业中的广泛应用及其在传统饮食中的核心地位，了解其化学组成和分布对于理解麸质饮食的复杂性至关重要。
1.2 人类与麸质的长期共生关系
人类与麸质的共生关系源远流长，其历史可以追溯到约10,000年前的新石器时代农业革命 910。在这一关键的历史转折点，人类社会从狩猎采集的生活方式逐渐转向定居农业，并开始大规模种植小麦、大麦等谷物 1112。这些富含碳水化合物的谷物不仅提供了稳定的食物来源，也为人口扩张和文明发展奠定了基础 10。小麦，作为全球最重要的谷类作物之一，其成功与其谷物蛋白——麸质——形成粘弹性面团的能力密不可分，这使得小麦粉能够被加工成多种多样的主食形式 13。
在新石器时代，虽然谷物带来了食物的丰裕和生活方式的转变，但也伴随着一些健康挑战。例如，与狩猎采集时代以蛋白质为主的饮食结构相比，谷物为主的饮食导致了龋齿等口腔疾病的增加 1415。然而，从整体上看，麸质谷物在人类饮食中扮演了核心角色，并随着农业的传播扩散到世界各地。小麦的栽培和食用历史长达约10,000年，从古老的二粒小麦、单粒小麦和斯佩尔特小麦，到现代大规模生产的高产品种，麸质谷物一直是人类重要的食物来源 1316。
遗传学研究也为人类与麸质的长期共生提供了间接证据。有研究发现，在以小麦为主要食物的地区，乳糜泻易感基因HLA-DQ2的频率与小麦消费量存在显著相关性 17。这表明，在这些长期食用麸质的地区，可能存在对麸质耐受性的选择压力，或者由于“人种扩散”效应，早期中东农民的基因随农业传播而扩散 17。
尽管传统饮食中麸质的长期摄入带来了诸多益处，例如支持了人口增长和文明发展，但进化论视角认为，人类基因组在进化时间尺度上对环境（包括饮食）变化的适应速度相对较慢 9。新石器时代和工业革命期间引入的食物主食和食品加工程序，从根本上改变了人类祖先饮食的七个关键营养特征，包括血糖负荷、脂肪酸组成、宏量营养素组成、微量营养素密度、酸碱平衡、钠钾比例和纤维含量 915。这种“进化冲突”被认为是许多西方文明慢性疾病的根源之一 9。然而，这些改变是否必然指向麸质本身对健康人群有害，则需要更严谨的科学证据来区分，而非简单归咎于人类与麸质的长期共生。在数千年的历史长河中，大多数人类群体在摄入麸质谷物的同时保持了相对健康的状态，这提示了在无麸质饮食争议中，需要区分特定疾病人群的需求与普通人群的健康管理。
2. 争议核心：麸质对健康影响的科学分歧
2.1 乳糜泻：明确病理机制下的无麸质治疗必要性
乳糜泻（Celiac Disease, CD）是一种由麸质引发的慢性自身免疫性疾病，发生于遗传易感个体中，其核心病理机制是麸质暴露导致小肠黏膜损伤，进而影响营养吸收 118。这种损伤的典型特征是绒毛萎缩、隐窝增生以及淋巴细胞浸润 19。全球流行病学数据显示，乳糜泻的患病率约为1%，且呈上升趋势，但仍有大量患者未被诊断 19202122。
乳糜泻的病理生理过程涉及复杂的免疫反应。当乳糜泻患者摄入麸质后，麸质中的醇溶谷蛋白肽段（特别是富含脯氨酸和谷氨酰胺的序列）在小肠内被组织转谷氨酰胺酶（tissue transglutaminase, tTG）脱酰胺化 118。脱酰胺化的麸质肽段随后被抗原呈递细胞（如树突状细胞）捕获，并呈递给具有特定HLA-DQ2或HLA-DQ8基因型（乳糜泻发病的必要遗传基础）的CD4+ T淋巴细胞 11823。这些T细胞被激活后，释放细胞因子（如干扰素-γ），引发一系列炎症反应，导致小肠黏膜损伤。同时，机体还会产生针对自身组织转谷氨酰胺酶的抗体（tTG-IgA抗体）和针对肌内膜的抗体（EMA），这些自身抗体是诊断乳糜泻的重要血清学标志物 12324。
由于麸质引发的免疫反应直接导致小肠黏膜受损，并可能引起多种胃肠道和肠外症状（如腹泻、腹痛、体重减轻、贫血、骨质疏松、皮肤病变等），甚至增加长期并发症（如营养不良、不孕、小肠淋巴瘤等）的风险，因此，严格的无麸质饮食（Gluten-Free Diet, GFD）是目前唯一有效且被广泛认可的治疗方法 1192526。无麸质饮食意味着终生避免所有含小麦、大麦、黑麦及其衍生成分的食物，以阻止免疫反应的持续激活，从而使受损的小肠黏膜得以修复，症状缓解，并降低并发症的风险 12527。
国际胃肠病学组织和多个国家及地区的权威机构，如欧洲乳糜泻研究学会（ESsCD）、美国胃肠病学会（AGA）等，均在其临床指南中强制推荐乳糜泻患者遵循严格的无麸质饮食 2627。例如，欧洲乳糜泻研究学会的指南明确指出，乳糜泻的诊断基于临床、血清学和组织病理学数据的结合，而无麸质饮食是主要的治疗手段，需要患者进行大量的教育、保持动机并进行随访 27。诊断乳糜泻通常需要进行血清学筛查（检测tTG-IgA和EMA抗体）和小肠活检以确认绒毛萎缩，且这些检查应在患者坚持麸质饮食的情况下进行，以避免假阴性结果 212327。一旦确诊，患者必须终生坚持无麸质饮食，因为即使是微量的麸质摄入也可能导致小肠损伤持续存在或复发 12526。有研究指出，无麸质饮食的依从性面临挑战，且并非所有患者都能完全响应，这促使学界探索新的非饮食治疗方案 202829。然而，在替代疗法被批准应用之前，无麸质饮食仍然是乳糜泻管理的基础和核心 1。
2.2 非乳糜泻麸质敏感（NCGS）：证据强度与诊断标准的争议
相较于乳糜泻明确的病理机制和诊断标准，非乳糜泻麸质敏感（Non-Celiac Gluten Sensitivity, NCGS）是一个更为复杂且充满争议的临床实体。NCGS指的是患者在摄入麸质后出现胃肠道或肠外症状，但排除了乳糜泻和小麦过敏的诊断，且症状在麸质清除饮食后改善，并在重新引入麸质后复发 3031323334。这一概念的出现，部分源于大量自称对麸质敏感但并非乳糜泻或小麦过敏的个体 32。
NCGS的临床表现具有多样性，既包括胃肠道症状，也包括肠外症状。常见的胃肠道症状与肠易激综合征（Irritable Bowel Syndrome, IBS）高度重叠，如腹痛、腹胀、腹泻或便秘 3334353637。一项针对韩国人群自报NCGS的调查显示，主要的胃肠道症状包括腹胀（75.0%）、腹部不适（71.3%）和嗳气（45.0%） 36。肠外症状则更为广泛，可包括疲劳、头痛、脑雾、关节疼痛、皮肤病变、情绪障碍等 32333638。韩国的调查发现，疲劳（20.0%）和头痛（13.7%）是常见的肠外症状 36。这些症状通常在摄入麸质后数小时或数天内出现，并在无麸质饮食后得到缓解 3233。
然而，NCGS的诊断面临巨大挑战，核心争议在于其证据强度和诊断标准的缺失 3134394041。目前，尚无特异性的生物标志物可用于NCGS的诊断 313338394142。这使得NCGS的诊断主要依赖于排除法和临床挑战试验，即在排除乳糜泻和小麦过敏后，通过严格的无麸质饮食观察症状改善，再通过双盲安慰剂对照（Double-Blind Placebo-Controlled, DBPC）麸质激发试验来确认症状的再现 31394043。
然而，DBPC麸质激发试验本身也存在诸多矛盾点：
- 安慰剂效应/反安慰剂效应（Nocebo Effect）的显著影响：多项研究表明，在自称NCGS的个体中，感知到的症状很大程度上受到反安慰剂效应的影响 35394445。一项国际多中心研究发现，仅预期摄入麸质（即使实际摄入的是安慰剂）就能导致显著的胃肠道症状，表明反安慰剂效应在NCGS患者的症状感知中扮演重要角色 44。这意味着，许多患者声称的“麸质敏感”症状，可能并非由麸质本身引起，而是由对麸质的负面预期所触发。这种效应使得NCGS的诊断更加复杂，难以区分真正的生理反应和心理暗示。
- 生物标志物的缺失：与乳糜泻的tTG-IgA抗体等明确生物标志物不同，NCGS缺乏可重复、敏感且特异的诊断标志物 313338394142。尽管一些研究探索了抗麦醇溶蛋白抗体（IgG AGA）、Zonulin（肠道通透性标志物）、微RNA以及某些细胞因子作为潜在标志物，但目前尚无被广泛接受的证据 32384142。这种缺失导致了诊断的困难和不同研究之间结果的可比性差。
- 诊断标准的非统一性：尽管2015年萨莱诺专家共识（Salerno Experts' Criteria）提出了DBPC麸质激发试验的诊断流程，包括8克/天的麸质挑战和症状评分标准（主要症状变化达到30%） 43，但这些标准在临床实践中的应用仍有限，且缺乏一致性 3439。这导致NCGS的流行病学数据高度不一，从自报的6%到基于严格诊断标准的0.6%不等 34。
此外，当前研究还广泛讨论了“麸质敏感”是否独立于其他食物成分。许多含麸质谷物（特别是小麦）除了麸质外，还含有其他可能引发胃肠道症状的成分，如可发酵的低聚糖、双糖、单糖和多元醇（FODMAPs）以及淀粉酶-胰蛋白酶抑制剂（ATIs） 3138424647。FODMAPs是短链碳水化合物，在肠道内难以消化吸收，容易被细菌发酵，导致产气和渗透压改变，从而引起腹胀、腹痛等IBS样症状 46。ATIs则可能通过激活先天免疫反应而引起症状 47。
因此，许多研究者认为，一些自报的“麸质敏感”症状可能实际上是对FODMAPs或ATIs的反应，而非麸质本身 38424647。这使得“非乳糜泻小麦敏感性”（Non-Celiac Wheat Sensitivity, NCWS）这一术语被提出，作为一个更广义的“伞式术语”，它涵盖了对麸质、FODMAPs或其他小麦成分的反应 384647。目前的证据倾向于将NCGS视为一种异质性疾病，包含不同的亚组，可能由不同的病理机制驱动 3241。未来的研究需要进一步阐明这些不同成分在NCGS样症状发生中的确切作用，并开发更精确的诊断方法，以区分真正的麸质敏感与其他食物成分敏感，从而为患者提供更精准的饮食管理建议。
2.3 健康人群限制麸质的潜在风险与收益悖论
近年来，无麸质饮食（GFD）的流行程度已远远超出其医学适应症（如乳糜泻和小麦过敏）的范围，许多健康人群也主动选择限制或完全避免麸质摄入，理由往往是认为这能改善消化、减轻体重、增加能量或普遍提升健康水平 48。然而，对于这些没有医学指征的健康个体而言，主动采取无麸质饮食可能面临一系列潜在的营养风险，并且其声称的健康收益往往缺乏确凿的科学证据支持，甚至可能适得其反，形成一种“收益悖论”。
营养缺口与潜在风险：
- B族维生素缺乏：传统含麸质谷物（如全麦）是B族维生素（如叶酸、硫胺素、烟酸）的重要来源。许多无麸质替代品（如大米粉、玉米淀粉、木薯粉）在加工过程中往往缺乏这些营养素，且较少进行营养强化。长期严格的无麸质饮食可能导致B族维生素摄入不足，影响能量代谢和神经功能 49。
- 膳食纤维不足：全谷物是膳食纤维的主要来源。无麸质饮食通常会排除小麦、大麦、黑麦等富含纤维的谷物，而无麸质加工食品（如无麸质面包、饼干）往往使用精制淀粉制成，纤维含量较低 49。膳食纤维的长期摄入不足可能导致便秘、肠道菌群失衡，并增加心血管疾病、2型糖尿病等风险。
- 矿物质缺乏：麸质谷物也是铁、锌、镁和钙等重要矿物质的良好来源。一项针对乳糜泻患者的研究显示，长期遵循无麸质饮食的患者可能出现铁、钙、镁和维生素D、E以及某些B族维生素的缺乏 49。健康人群若非基于医学需要而采取无麸质饮食，也面临类似的风险，可能导致贫血、骨密度下降等问题。
- 蛋白质和微量元素不均衡：一些无麸质饮食者倾向于选择加工过的无麸质产品，这些产品通常糖、脂肪含量较高，而蛋白质、维生素和矿物质含量相对较低，导致饮食结构不均衡 50。
与代谢综合征、肠道菌群紊乱的关联风险：
多项研究关注了无麸质饮食对健康人群（特别是无乳糜泻的个体）代谢健康的影响：
- 体重增加和代谢综合征风险：尽管许多人选择无麸质饮食是为了减肥，但部分研究发现，对于乳糜泻患者而言，在开始无麸质饮食后体重增加甚至出现超重/肥胖的频率有所增加 50。这可能与无麸质加工食品为了改善口感而添加更多的糖、脂肪以及较低的膳食纤维有关 5152。一项对乳糜泻患者的研究发现，他们在开始无麸质饮食12个月后，代谢综合征的患病率从2%显著增加到29.5%，其中腰围增大、血压升高和血糖升高尤为明显 53。虽然这项研究是针对乳糜泻患者的，但其揭示的无麸质饮食可能带来的代谢风险，对于健康人群同样具有警示意义。另一项针对代谢综合征患者的随机对照试验显示，短期（8周）无麸质饮食能够降低腰围、改善血糖控制和甘油三酯水平，但对LDL胆固醇、总胆固醇、空腹胰岛素、血压等无显著影响 54。这提示无麸质饮食对代谢指标的影响是复杂的，且可能因个体和持续时间而异。
- 肠道菌群紊乱：膳食纤维是肠道益生菌的重要“食物”。如前所述，无麸质饮食常导致膳食纤维摄入减少，这可能对肠道微生物组成产生负面影响，导致肠道菌群多样性降低或益生菌数量减少 5556。肠道菌群失衡（dysbiosis）已被证实与多种慢性疾病相关，包括炎症性肠病、肥胖、2型糖尿病甚至一些神经精神疾病 5557。
- 对心血管健康的争议：尽管一些患者认为无麸质饮食可能改善心血管风险因素，但目前的证据尚不明确。有综述指出，虽然该饮食可能轻微改善总体心脏风险因素、体重或胰岛素抵抗，但在没有麸质相关疾病的情况下使用该饮食是存在争议的 58。
综上所述，对于健康人群而言，主动限制麸质并没有明确的健康收益，反而可能带来营养不良的风险，并潜在影响代谢健康和肠道菌群平衡。除非有明确的医学诊断，否则不建议健康个体盲目跟风无麸质饮食潮流。相反，应鼓励食用均衡的、富含全谷物、水果、蔬菜和健康脂肪的饮食模式。
3. 争议扩散：社会认知与商业市场的推波助澜
3.1 媒体传播与公众认知偏差
在科学界对麸质饮食的健康效益存在争议的同时，媒体和社交平台对“无麸质”概念的传播起到了推波助澜的作用，极大影响了公众对麸质的认知，并常常导致科学信息的误读和偏差。“无麸质=健康”这一标签，在很多情况下并非来源于严谨的医学研究，而是通过大众媒体和社交平台，从一个医学术语逐渐演变为一种广受欢迎的“网红”饮食概念，甚至被赋予了减肥、排毒、提升精力的光环。
这种演变路径主要体现在以下几个方面：
- 医学术语的“去语境化”与流行化：乳糜泻患者对无麸质饮食的严格需求，是基于明确的病理机制和临床证据。然而，当这一医学术语被大众媒体报道时，其复杂的医学背景往往被简化甚至省略，只留下“无麸质有益健康”的表象。例如，媒体可能报道某名人通过无麸质饮食成功减重或改善健康状况，这使得公众将无麸质饮食与普遍的健康益处划上等号，而忽略了其原有的医疗适用性。这种“去语境化”的传播，使得医学建议被过度泛化，最终形成“无麸质是健康潮流”的公众认知。
- 社交媒体中的“麸质有害论”：社交媒体平台（如微博、抖音、小红书、Twitter、Instagram等）为个人用户提供了极大的信息发布自由，使得“麸质有害论”得以迅速扩散，成为一种典型的科学误读机制。
- 非专业人士的主导性内容生产：研究显示，在YouTube等视频平台，关于无麸质饮食的内容数量呈上升趋势，但视频整体质量普遍较差，多数不够严谨，且大多数内容由非专业人士（如患者或普通用户）发布，健康专业人士发布的内容质量虽高，但占比很小 59。同样，在Twitter上，关于乳糜泻和无麸质饮食的大部分内容由自我推销者（如博主、作家）、商业实体（如餐厅和面包店）或自称的家庭成员（如母亲）发布，而自我认定的科学、非营利组织和医疗服务提供者的贡献相对较少 60。这种信息源的结构性问题导致了大量未经证实或误导性的信息充斥其中。
- “带货”与商业利益驱动：部分社交媒体内容以“健康专家”、“生活博主”的身份，将无麸质饮食与某种特定的生活方式或产品绑定，推广无麸质食品或补剂，形成商业闭环。这种“带货”模式模糊了健康信息与商业宣传的界限，使得“无麸质”标签更具吸引力，甚至被视为一种时尚或社会地位的象征。
- 经验分享替代科学证据：社交媒体鼓励个人经验的分享，对于许多饱受非特异性症状困扰的个体而言，看到他人通过无麸质饮食获得“改善”的案例，容易产生共鸣并效仿，即使这些“改善”可能仅仅是安慰剂效应。例如，有研究发现，在Instagram上关于银屑病（Psoriasis）饮食管理的信息，多数由有亲身经历的患者（29.7%）发布，而非合格的营养师或医疗专业人员，且大部分帖子质量低下，含有误导性信息，如建议无麸质饮食 6162。这反映出，当专业知识的传播不足时，公众更容易被个体经验所吸引，而非基于证据的建议。
- 缺乏批判性思维的受众：在信息爆炸的时代，公众往往缺乏识别虚假或误导性健康信息的能力。对于复杂的科学概念，简单、直接且带有情感色彩的故事更容易被接受和传播，而非严谨的科学解释。
这些媒体传播机制共同塑造了“麸质有害论”的社会认知，使得许多健康人群在没有医学必要性的情况下，盲目跟风无麸质饮食。这种认知偏差不仅浪费了社会资源，也可能导致个人营养不均衡和不必要的心理负担。
3.2 无麸质食品市场的扩张与监管挑战
在“无麸质=健康”的公众认知和媒体推波助澜下，全球无麸质食品市场呈现出爆发式增长的态势。这一市场扩张不仅是为了满足乳糜泻患者的刚性需求，更是迎合了大量健康人群对“健康”、“天然”和“瘦身”的追求。
无麸质食品市场规模增长数据：
根据多项市场研究报告，全球无麸质食品市场在过去十年中实现了显著增长。例如，有数据显示，2015年至2025年期间，全球无麸质食品市场的复合年增长率（CAGR）预计将达到8%至10%左右，市场规模在未来几年有望突破百亿美元大关。驱动这一增长的主要因素包括：乳糜泻诊断率的提升、非乳糜泻麸质敏感人群的增加（尽管诊断标准仍有争议）、健康意识的普遍提高以及食品行业在新产品开发上的投入。
这种增长反映在超市货架上无麸质产品种类和数量的激增，从传统的面包、饼干、面条，到零食、调味品乃至啤酒，无麸质标签几乎渗透到所有食品类别中。
产品标签规范与“无麸质”阈值标准：
无麸质食品市场的快速发展，使得产品标签的规范和“无麸质”标准的界定成为监管机构面临的重要挑战。核心问题在于，如何确保标示“无麸质”的产品真正安全，特别是对于乳糜泻患者而言，即使是微量的麸质也可能引发健康问题。
国际上普遍接受的“无麸质”标准是产品中麸质含量不超过20 ppm（百万分之一，即每千克食物中含有不超过20毫克的麸质）6364。这一标准由国际食品法典委员会（Codex Alimentarius Commission）于2008年设定，并被许多国家和地区采纳。
- 美国食品药品监督管理局（FDA）：FDA要求在美国市场销售的、声称“无麸质”的食品，其麸质含量不得超过20 ppm 6364。此外，FDA还规定，食品标签上若带有“无麸质”（gluten-free）、“不含麸质”（no gluten）、“不含小麦”（free of gluten）、“不含任何麸质成分”（without gluten）等宣称，都必须满足这一标准。这项规定旨在保护乳糜泻患者，并帮助消费者做出知情的选择 64。
- 欧盟食品安全局（EFSA）：欧盟也采纳了20 ppm的麸质阈值标准。此外，欧盟对于“非常低麸质”（very low gluten）的产品也设立了标准，即麸质含量不超过100 ppm。
- 其他国家和地区：许多其他国家和地区，如加拿大、澳大利亚、新西兰等，也基本遵循或借鉴了20 ppm的国际标准。
尽管有统一的阈值标准，但在实际检测和监管中仍存在挑战：
- 检测方法的局限性：目前，酶联免疫吸附测定（ELISA）是检测食品中麸质含量的主要方法，特别是R5抗体ELISA方法被广泛推荐 6566。然而，由于麸质蛋白的复杂性、食品加工过程（如发酵、水解）对麸质结构的影响，以及不同ELISA试剂盒之间抗体特异性和灵敏度的差异，准确量化发酵水解食品中的麸质仍然是一个挑战 636768。例如，发酵和水解过程可能改变麸质蛋白的抗原性，导致传统ELISA方法难以准确检测 63。
- 交叉污染问题：即使是声称“无麸质”的产品，在生产、运输和储存过程中也可能发生交叉污染，导致微量麸质的存在。这对于生产企业提出了更高的要求，需要严格控制生产线和供应链，以确保产品符合标准。
- 不同麸质来源的检测差异：小麦、黑麦和大麦中的麸质蛋白组成有所不同，不同ELISA试剂盒对这些不同来源的麸质的检测灵敏度也存在差异 6568。这意味着某些试剂盒可能对特定来源的麸质检测不足，从而给消费者带来潜在风险。
营养宣称的监管现状：
除了“无麸质”标签，许多无麸质食品还会附带其他营养宣称，如“高纤维”、“低脂”等。这些营养宣称的监管同样重要，以防止误导性营销。
- 对消费者感知的影响：消费者普遍认为带有营养宣称的食品更健康 69。例如，研究发现“健康感”积极影响了消费者购买带有营养宣称食品的意愿。这种认知使得制造商更倾向于在无麸质产品上添加健康宣称，以吸引消费者。
- 监管机构的立场：FDA和EFSA等机构不仅监管“无麸质”标签，也对其他营养宣称有严格规定，要求这些宣称必须有科学依据，且不得夸大其词或误导消费者。例如，如果一个无麸质产品宣称“富含膳食纤维”，那么其膳食纤维含量必须达到法规规定的标准。然而，在实际操作中，一些无麸质产品为了改善口感或延长保质期，往往会添加更多的糖、脂肪或精制淀粉，导致其整体营养价值可能低于传统含麸质的同类产品，这给监管带来了挑战。
- 全球差异：虽然主要监管机构在“无麸质”阈值上趋于一致，但在营养宣称的详细规定和执行力度上可能存在差异。一项针对全球麸质专家进行的调查显示，与高收入国家相比，中低收入国家在无麸质食品的可获得性、质量以及标签立法方面存在显著差距 70。这表明全球范围内的监管水平并不均衡，部分地区可能面临更大的挑战。
总之，无麸质食品市场的繁荣反映了消费者对健康饮食的日益关注，但同时也对食品安全监管提出了更高要求。监管机构需不断完善标准、提升检测技术、加强市场监督，以确保消费者能获得真正安全、有益且信息透明的无麸质产品。
4. 争议的科学共识与未来研究方向
4.1 当前学界的基本共识框架
尽管围绕麸质饮食的争议甚嚣尘上，但全球权威医学和营养学机构已就麸质摄入对不同人群的影响形成了基本共识。这些共识强调了基于科学证据的个体化饮食管理，而非盲目追随潮流。
1. 乳糜泻（Celiac Disease）患者：严格且终生无麸质饮食是强制性治疗方案。
这是学界最明确、最无争议的共识。世界胃肠病组织（World Gastroenterology Organisation, WGO）、美国胃肠病学会（American College of Gastroenterology, ACG）和欧洲儿科胃肠病学、肝病学和营养学会（ESPGHAN）等机构均一致推荐乳糜泻患者必须严格遵守无麸质饮食。这是因为麸质会触发这些患者的自身免疫反应，导致小肠损伤和吸收不良，并增加长期并发症的风险 27717273。无麸质饮食是目前唯一有效的治疗方法，可促进肠道修复、症状缓解和生活质量改善 7174。任何微量的麸质摄入都可能导致肠道损伤的持续存在或复发，因此，对于乳糜泻患者而言，无麸质饮食不是选择，而是必须 7172。
2. 小麦过敏（Wheat Allergy）患者：需避免小麦及其制品。
小麦过敏是一种IgE介导的免疫反应，与乳糜泻的自身免疫机制不同，但同样需要避免致敏原。由于小麦是主要的麸质来源，因此小麦过敏患者也需避免含有小麦麸质的食物。
3. 非乳糜泻麸质敏感（Non-Celiac Gluten Sensitivity, NCGS）患者：个体化评估与饮食管理。
对于NCGS，学界的共识是其存在性已被初步承认，但其诊断标准、病理机制及麸质在其症状中的确切作用仍有待深入研究 75。由于目前缺乏特异性生物标志物，诊断主要依赖于排除乳糜泻和小麦过敏后的双盲安慰剂对照麸质激发试验 75。权威机构建议，对于怀疑NCGS的患者，应在专业医生和注册营养师的指导下进行个体化评估，包括排除性诊断和严格的食物激发试验，以确定是否确实对麸质敏感，或者症状是否由FODMAPs或其他食物成分引起 7677。不建议NCGS患者在未确诊的情况下盲目长期坚持无麸质饮食，因为这可能导致营养缺乏 78。
4. 健康人群：无需限制麸质摄入。
这是与公众认知偏差最大的共识点。权威机构明确指出，对于没有乳糜泻、小麦过敏或确诊NCGS的健康个体而言，没有证据表明无麸质饮食能带来额外的健康益处，如减肥、改善消化或提升能量水平 74。相反，如前所述，健康人群在没有医学指导的情况下采取无麸质饮食，可能导致膳食纤维、B族维生素、铁、钙等重要营养素的摄入不足，甚至可能影响肠道菌群平衡，带来潜在的健康风险 78。例如，专家共识指出，在评估健康饮食和饮食质量指数时，麸质并非普遍的风险因素，而水果、蔬菜、乳制品、豆类和油籽被认为是膳食质量的积极指标 79。因此，对于健康人群，均衡的膳食，包括适量摄入全谷物，才是促进健康的最佳途径。
4.2 争议解决的关键研究方向
尽管当前学界对麸质饮食的健康影响已形成基本共识，但要彻底解决围绕麸质的诸多争议，仍需要深入的科学研究来填补知识空白。未来的研究应重点关注以下几个关键方向：
NCGS特异性生物标志物开发：
非乳糜泻麸质敏感（NCGS）是当前麸质争议中最具挑战性的领域。其缺乏明确的诊断标准和客观的生物标志物，使得临床诊断困难重重，也阻碍了对NCGS发病机制的深入理解 38。现有研究虽然探索了一些潜在的标志物，例如抗麦醇溶蛋白抗体（IgG AGA）、肠道通透性标志物Zonulin、特定的微RNA（micro-RNA）和长链非编码RNA（lncRNA），以及某些细胞因子等 323880，但这些标志物的特异性和敏感性仍不足以支持临床诊断。
未来的研究应致力于通过整合多组学技术（如基因组学、蛋白质组学、代谢组学和微生物组学），识别出能够特异性区分NCGS患者与其他麸质相关疾病（如乳糜泻、小麦过敏）及功能性胃肠道疾病（如肠易激综合征）的分子指纹。例如，可以深入研究麸质或小麦中非麸质成分（如FODMAPs、ATIs）在NCGS患者体内引发的免疫反应、肠道屏障功能改变以及肠道微生物组成和功能的特异性变化 38。开发出稳定、可重复且易于临床应用的生物标志物，将是NCGS诊断和管理领域的重大突破，有助于减少误诊和过度饮食限制，并为精准医疗奠定基础。长期无麸质饮食对普通人群的代谢影响追踪：
随着无麸质饮食在健康人群中日益普及，迫切需要大样本、长期随访的队列研究，系统性评估其对非乳糜泻或非小麦过敏的普通人群的代谢健康、肠道菌群和营养状况的长期影响。尽管已有研究提示，无麸质饮食可能导致某些营养素（如B族维生素、膳食纤维、铁、锌）的缺乏，并可能与代谢综合征风险增加有关，但这些证据主要来源于对乳糜泻患者的研究或规模较小的短期干预试验。
未来的研究应通过设计严格的随机对照试验和前瞻性队列研究，对比健康人群中长期无麸质饮食与传统均衡饮食对血糖、血脂、体重、心血管健康指标、炎症标志物以及肠道菌群多样性和功能的影响。重点关注无麸质食品中营养成分的再评估，以及其高糖、高脂肪特性对整体饮食质量的潜在负面作用。此类研究将提供确凿的科学依据，指导健康人群的膳食选择，避免不必要的饮食限制带来的潜在健康风险。麸质免疫原性的个体差异遗传机制：
为何有些人对麸质敏感，而另一些人则能良好耐受？这其中的遗传和表观遗传机制仍不完全清楚。尽管已知HLA-DQ2和HLA-DQ8基因型是乳糜泻发病的必要条件，但并非所有携带这些基因型的人都会发展为乳糜泻，这提示存在其他遗传或环境因素的相互作用 81。
未来的研究应深入探讨麸质免疫原性的个体差异，包括：- 非HLA基因的作用：除了主要的HLA基因，还存在哪些非HLA基因位点参与调控对麸质的免疫反应和肠道屏障功能？
- 肠道微生物组的影响：肠道菌群在麸质消化、免疫调节以及宿主对麸质反应中的作用日益受到关注 81。研究应进一步阐明特定肠道菌群结构或功能是否会影响麸质肽段的降解、肠道通透性以及宿主的免疫耐受性，从而影响个体对麸质的敏感性。
- 环境因素与基因-环境相互作用：早期生命阶段的饮食、感染、抗生素使用等环境因素如何与遗传背景相互作用，共同决定个体成年后对麸质的反应？
通过解析麸质免疫原性的复杂遗传和环境交互网络，将有助于更精确地识别高风险人群，并为开发个性化预防和治疗策略提供新思路，例如通过基因检测预测麸质敏感性，或通过调节肠道菌群来增强麸质耐受性。
这些研究方向的突破将不仅深化我们对麸质相关疾病的理解，也有助于为公众提供更明确、基于证据的膳食建议，从而有效应对当前围绕麸质饮食的科学争议和社会挑战。
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参考文献
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Giacomo Caio, Umberto Volta, Anna Sapone, et al.
BMC Med. 2019 Jul 23;17(1):142. doi: 10.1186/s12916-019-1380-z.
BACKGROUND: Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY: A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS: The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
2Wheat gluten: high molecular weight glutenin subunits--structure, genetics, and relation to dough elasticity.PubMed
Faqir Muhammad Anjum, Moazzam Rafiq Khan, Ahmad Din, et al.
J Food Sci. 2007 Apr;72(3):R56-63. doi: 10.1111/j.1750-3841.2007.00292.x.
Gluten proteins, representing the major protein fraction of the starchy endosperm, are predominantly responsible for the unique position of wheat amongst cereals. These form a continuous proteinaceous matrix in the cells of the mature dry grain and form a continuous viscoelastic network during the mixing process of dough development. These viscoelastic properties underline the utilization of wheat to prepare bread and other wheat flour based foodstuffs. One group of gluten proteins is glutenin, which consists of high molecular weight (HMW) and low molecular weight (LMW) subunits. The HMW glutenin subunits (HMW-GS) are particularly important for determining dough elasticity. The common wheat possesses 3 to 5 HMW subunits encoded at the Glu-1 loci on the long arms of group 1 chromosomes (1A, 1B, and 1D). The presence of certain HMW subunits is positively correlated with good bread-making quality. Glutamine-rich repetitive sequences that comprise the central part of the HMW subunits are actually responsible for the elastic properties due to extensive arrays of interchain hydrogen bonds. Genetic engineering can be used to manipulate the amount and composition of the HMW subunits, leading to either increased dough strength or more drastic changes in gluten structure and properties.
3The structure and properties of gluten: an elastic protein from wheat grain.PubMed
Peter R Shewry, Nigel G Halford, Peter S Belton, et al.
Philos Trans R Soc Lond B Biol Sci. 2002 Feb 28;357(1418):133-42. doi: 10.1098/rstb.2001.1024.
The wheat gluten proteins correspond to the major storage proteins that are deposited in the starchy endosperm cells of the developing grain. These form a continuous proteinaceous matrix in the cells of the mature dry grain and are brought together to form a continuous viscoelastic network when flour is mixed with water to form dough. These viscoelastic properties underpin the utilization of wheat to give bread and other processed foods. One group of gluten proteins, the HMM subunits of glutenin, is particularly important in conferring high levels of elasticity (i.e. dough strength). These proteins are present in HMM polymers that are stabilized by disulphide bonds and are considered to form the 'elastic backbone' of gluten. However, the glutamine-rich repetitive sequences that comprise the central parts of the HMM subunits also form extensive arrays of interchain hydrogen bonds that may contribute to the elastic properties via a 'loop and train' mechanism. Genetic engineering can be used to manipulate the amount and composition of the HMM subunits, leading to either increased dough strength or to more drastic changes in gluten structure and properties.
4What is gluten?PubMed
Jessica R Biesiekierski
J Gastroenterol Hepatol. 2017 Mar;32 Suppl 1:78-81. doi: 10.1111/jgh.13703.
Gluten is the main storage protein of wheat grains. Gluten is a complex mixture of hundreds of related but distinct proteins, mainly gliadin and glutenin. Similar storage proteins exist as secalin in rye, hordein in barley, and avenins in oats and are collectively referred to as "gluten." The objective was to discuss the biochemical and functional properties of the gluten proteins, including structure, sources, and dietary intakes. Literature was reviewed from food science and nutrition journals. The gluten protein networks vary because of different components and sizes, and variability caused by genotype, growing conditions, and technological processes. The structures and interactions of this matrix contribute to the unique properties of gluten. The resulting functions are essential to determining the dough quality of bread and other baked products. Gluten is heat stable and has the capacity to act as a binding and extending agent and is commonly used as an additive in processed foods for improved texture, moisture retention, and flavor. Gliadin contains peptide sequences that are highly resistant to gastric, pancreatic, and intestinal proteolytic digestion in the gastrointestinal tract. The average daily gluten intake in a Western diet is thought to be 5-20 g/day and has been implicated in several disorders. Gluten containing grains (wheat, rye, barley, and oats) are important staple foods. Gluten is among the most complex protein networks and plays a key role in determining the rheological dough properties.
5Chemistry of gluten proteins.PubMed
Herbert Wieser
Food Microbiol. 2007 Apr;24(2):115-9. doi: 10.1016/j.fm.2006.07.004. Epub 2006 Sep 7.
Gluten proteins play a key role in determining the unique baking quality of wheat by conferring water absorption capacity, cohesivity, viscosity and elasticity on dough. Gluten proteins can be divided into two main fractions according to their solubility in aqueous alcohols: the soluble gliadins and the insoluble glutenins. Both fractions consist of numerous, partially closely related protein components characterized by high glutamine and proline contents. Gliadins are mainly monomeric proteins with molecular weights (MWs) around 28,000-55,000 and can be classified according to their different primary structures into the alpha/beta-, gamma- and omega-type. Disulphide bonds are either absent or present as intrachain crosslinks. The glutenin fraction comprises aggregated proteins linked by interchain disulphide bonds; they have a varying size ranging from about 500,000 to more than 10 million. After reduction of disulphide bonds, the resulting glutenin subunits show a solubility in aqueous alcohols similar to gliadins. Based on primary structure, glutenin subunits have been divided into the high-molecular-weight (HMW) subunits (MW=67,000-88,000) and low-molecular-weight (LMW) subunits (MW=32,000-35,000). Each gluten protein type consists or two or three different structural domains; one of them contains unique repetitive sequences rich in glutamine and proline. Native glutenins are composed of a backbone formed by HMW subunit polymers and of LMW subunit polymers branched off from HMW subunits. Non-covalent bonds such as hydrogen bonds, ionic bonds and hydrophobic bonds are important for the aggregation of gliadins and glutenins and implicate structure and physical properties of dough.
6Molecular insights into the role of amylose/amylopectin ratio on gluten protein organization.PubMed
Davide Emide, Chiara Magni, Francesca Saitta, et al.
Food Chem. 2023 Mar 15;404(Pt B):134675. doi: 10.1016/j.foodchem.2022.134675. Epub 2022 Oct 20.
Waxy (WX) and high-amylose (HA) wheat flours have interesting functional and/or nutritional characteristics, but low technological properties compared to regular wheat. Here a set of three wheat lines, having different amylose content but sharing the same varietal background, were compared to shed light on the role of the amylose/amylopectin ratio on the protein conformational changes that lead to gluten formation. Despite the absence of differences in their protein profile, as also confirmed by thiolomic approaches, both WX and HA lines developed a weaker gluten than the control sample. The altered amylose/amylopectin ratio exerts a matrix effect establishing a competition for water with proteins, leading to a different protein structure and three-dimensional organization of the gluten network. These results add a piece to the understanding of the molecular aspects that oversee matrix effects on gluten formation in wheat, which description can be helpful for a rational optimization of the transformation process.
7Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities.PubMed
Anastasia V Balakireva, Andrey A Zamyatnin
Nutrients. 2016 Oct 18;8(10):644. doi: 10.3390/nu8100644.
Theterm gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten can be subdivided into three major groups: S-rich, S-poor and high molecular weight proteins. Prolamins within the groups possess similar structures and properties. All gluten proteins are evolutionarily connected and share the same ancestral origin. Gluten proteins are highly resistant to hydrolysis mediated by proteases of the human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. Nowadays, there are several ways to detoxify gluten peptides: the most common is gluten-free diet (GFD), which has proved its effectiveness; prevention programs, enzymatic therapy, correction of gluten pathogenicity pathways and genetically modified grains with reduced immunotoxicity. A deep understanding of gluten intolerance underlying mechanisms and detailed knowledge of gluten properties may lead to the emergence of novel effective approaches for treatment of gluten-related disorders.
8Wheat gluten amyloid fibrils: Conditions, mechanism, characterization, application, and future perspectives.PubMed
Huijuan Zhang, Shihao Lv, Chengming Jin, et al.
Int J Biol Macromol. 2023 Dec 31;253(Pt 3):126435. doi: 10.1016/j.ijbiomac.2023.126435. Epub 2023 Aug 21.
Amyloid fibrils have excellent structural characteristics, such as a high aspect ratio, excellent stiffness, and a wide availability of functional groups on the surface. More studies are now focusing on the formation of amyloid fibrils using food proteins. Protein fibrillation is now becoming recognized as a promising strategy for enhancing the function of food proteins and expanding their range of applications. Wheat gluten is rich in glutamine (Q), hydrophobic amino acids, and the α-helix structure with high β-sheet tendency. These characteristics make it very easy for wheat gluten to form amyloid fibrils. The conditions, formation mechanism, characterization methods, and application of amyloid fibrils formed by wheat gluten are summarized in this review. Further exploration of amyloid fibrils formed by wheat gluten will reveal how they can play a significant role in food, biology, and other fields, especially in medicine.
9Origins and evolution of the Western diet: health implications for the 21st century.PubMed
Loren Cordain, S Boyd Eaton, Anthony Sebastian, et al.
Am J Clin Nutr. 2005 Feb;81(2):341-54. doi: 10.1093/ajcn.81.2.341.
There is growing awareness that the profound changes in the environment (eg, in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry approximately 10000 y ago occurred too recently on an evolutionary time scale for the human genome to adjust. In conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns of contemporary Western populations, many of the so-called diseases of civilization have emerged. In particular, food staples and food-processing procedures introduced during the Neolithic and Industrial Periods have fundamentally altered 7 crucial nutritional characteristics of ancestral hominin diets: 1) glycemic load, 2) fatty acid composition, 3) macronutrient composition, 4) micronutrient density, 5) acid-base balance, 6) sodium-potassium ratio, and 7) fiber content. The evolutionary collision of our ancient genome with the nutritional qualities of recently introduced foods may underlie many of the chronic diseases of Western civilization.
10Microbiome and Health: Ramifications of Intelligent Deception.PubMed
George B Stefano, Rachel Fine, Richard M Kream
Med Sci Monit. 2018 Apr 7;24:2060-2062. doi: 10.12659/msm.910248.
Ten thousand years ago, the foundation for agricultural development and animal domestication was laid. Neolithic founder crops were carbohydrate-laden cereal grasses that facilitated transformation of hunter-gather societies into ancient civilizations with realistic capabilities for population expansion. In the last 3-4 decades, however, debilitating medical consequences of a progressively narrowed high caloric diet incorporating processed carbohydrates, animal protein, saturated fat and cholesterol, are translated into a global epidemic of obesity linked to metabolic and endocrine disorders, which, in part, emerged from the enhancement of our longevity. The initiation and progression of pathophysiological processes associated with this restrictive diet may well reside in the gastrointestinal tract. The critical role of human gut microbiome in facilitating normal gut physiology and linkages to other physiological systems points to its significance in comorbid pathologies when its diversity is compromised. Cortical desensitization to the potentially damaging effects of intentionally restricted high carbohydrate diets is progressively enhanced by compromised metabolic activities and widespread pro-inflammatory processes within all organ systems. Our cognitive ability must overcome the desire for comfort foods. The solution is simple: minimize "processed" foods and those of similar commercial origin in our diet, restoring a more diverse gut microbiome. Initially the solution may be costly, however, within the scope of sustained healthy longevity it will "payoff".
11Human adaptations to diet: Biological and cultural coevolution.PubMed
Aline Jelenkovic, María Eugenia Ibáñez-Zamacona, Esther Rebato
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Modern humans evolved in Africa some 200,000 years ago, and since then, human populations have expanded and diversified to occupy a broad range of habitats and use different subsistence modes. This has resulted in different adaptations, such as differential responses to diseases and different abilities to digest or tolerate certain foods. The shift from a subsistence strategy based on hunting and gathering during the Palaeolithic to a lifestyle based on the consumption of domesticated animals and plants in the Neolithic can be considered one of the most important dietary transitions of Homo sapiens. In this text, we review four examples of gene-culture coevolution: (i) the persistence of the enzyme lactase after weaning, which allows the digestion of milk in adulthood, related to the emergence of dairy farming during the Neolithic; (ii) the population differences in alcohol susceptibility, in particular the ethanol intolerance of Asian populations due to the increased accumulation of the toxic acetaldehyde, related to the spread of rice domestication; (iii) the maintenance of gluten intolerance (celiac disease) with the subsequent reduced fitness of its sufferers, related to the emergence of agriculture and (iv) the considerable variation in the biosynthetic pathway of long-chain polyunsaturated fatty acids in native populations with extreme diets.
12Prebiotics in obesity.PubMed
S Carnahan, A Balzer, S K Panchal, et al.
Panminerva Med. 2014 Jun;56(2):165-75. Epub 2014 May 20.
Obesity was probably rare in ancient times, with the current increase starting in the Industrial Revolution of the eighteenth century, and becoming much more widespread from about 1950, so concurrent with the increased consumption of carbohydrates from cereals in the Green Revolution. However, dietary components such as oligosaccharides from plants including cereals may improve health following fermentation to short-chain carboxylic acids in the intestine by bacteria which constitute of the microbiome. Such non-digestible and fermentable components of diet, called prebiotics, have been part of the human diet since at least Palaeolithic times, and include components of the cereals domesticated in the Neolithic Revolution. If consumption of these cereals has now increased, why is obesity increasing? One reason could be lowered prebiotic intake combined with increased intake of simple sugars, thus changing the bacteria in the microbiome. Processing of food has played an important role in this change of diet composition. Since obesity is a low-grade inflammation, changing the microbiome by increased consumption of simple carbohydrates and saturated fats may lead to obesity via increased systemic inflammation. Conversely, there is now reasonable evidence that increased dietary prebiotic intake decreases inflammation, improves glucose metabolism and decreases obesity. Would widespread increases in prebiotics in the modern diet, so mimicking Palaeolithic or Neolithic nutrition, decrease the incidence and morbidity of obesity in our communities?
13The 10,000-Year Success Story of Wheat!PubMed
Telma de Sousa, Miguel Ribeiro, Carolina Sabença, et al.
Foods. 2021 Sep 8;10(9):2124. doi: 10.3390/foods10092124.
Wheat is one of the most important cereal crops in the world as it is used in the production of a diverse range of traditional and modern processed foods. The ancient varieties einkorn, emmer, and spelt not only played an important role as a source of food but became the ancestors of the modern varieties currently grown worldwide. Hexaploid wheat ( L.) and tetraploid wheat ( Desf.) now account for around 95% and 5% of the world production, respectively. The success of this cereal is inextricably associated with the capacity of its grain proteins, the gluten, to form a viscoelastic dough that allows the transformation of wheat flour into a wide variety of staple forms of food in the human diet. This review aims to give a holistic view of the temporal and proteogenomic evolution of wheat from its domestication to the massively produced high-yield crop of our day.
14Dental worm disease.PubMed
Sergio Sabbatani, Sirio Fiorino
Infez Med. 2016 Dec 1;24(4):349-358.
During human evolution, the period in which groups of humans stopped harvesting fruits and seeds growing wild and introduced the cultivation of cereals as well as the domestication of animals represents a very important event. This circumstance had a considerable impact on human pathocenosis, increasing the risk of infectious diseases of animal origin. The aim of this review was to summarise the archaeological and palaeo-pathological evidence in the literature concerning this topic. Starting from early prehistory (about 1.5 million years ago) up to the historical period, several authors have described the changes in human habits and the consequent changes in food supply, leading to the transition from a protein- to a carbohydrate-rich diet across a broad interval of time. This led to additional problems for human health. The increased accumulation of carbohydrate debris in the odonto-stomatological apparatus, without the appropriate use of hygiene in the oral cavity, increased the risk of infectious disease involving the mouth. Therefore, since the Neolithic period there has been a higher risk of tooth caries, abscesses, deep infection of the teeth roots, reaching also the mandibular and maxillary bone. Several hypotheses have been proposed by the distinct civilizations, which have alternated in the different ages, to explain the cause of these human health problems, including the idea that a "dental worm" could be involved in this process, such as in the Sumerian period. We describe and discuss further modifications of this theory, developed in Egypt, Assyria, Babylon, China, Greece, in Etruscan cities and in Rome in ancient times as well as in the Middle Ages, and the evolution of scientific thought on this topic in the past 300 years. In addition, the results of some palaeo-pathological studies, which were performed on human remains, such as the maxillary bone and teeth, mainly in different geographical areas in Italy, are examined and reported.
15The Impact of Diet and Nutrition on the Oral Microbiome.PubMed
Simona Santonocito, Alessandro Polizzi, Gaetano Isola
Adv Exp Med Biol. 2025;1472:53-69. doi: 10.1007/978-3-031-79146-8_4.
At present, it is well known that oral health is essential for the well-being of the body as a whole, thanks to the increasing awareness of how various oral diseases, including periodontal disease, oral carcinomas, and other conditions, have a close connection with various systemic disorders. In recent decades, studies on the oral microbiome have increasingly emphasized how the balance between the host and the microbial species that coexist there is essential for oral health at all stages of life. However, there are many factors capable of interfering with that balance, and diet is precisely one of them. The real influence of diet on the oral microbiota, and consequently on oral health, has been much debated. In this context, the observation of two key periods in human history, the Neolithic and the Industrial Revolution, has proved to be diriment. The foods and processing techniques that emerged in these two historical periods, in association with changes in customs and habits, significantly altered the central constituents of the human diet, including macronutrient proportions, glycemic load, fatty acid composition, sodium and potassium levels, micronutrient levels, dietary pH, and fiber content taken in by human beings. The introduction of these foods into the daily human routine has been linked to a decline in oral health and an increase of several other diseases, including cardiovascular diseases, inflammatory bowel disease, rheumatic diseases, many cancers, and obesity. The aim of this chapter is to update the current knowledge and further discuss the role of diet and nutrition on oral health.
16From ancient to old and modern durum wheat varieties: interaction among cultivar traits, management, and technological quality.PubMed
Marina Mefleh, Paola Conte, Costantino Fadda, et al.
J Sci Food Agric. 2019 Mar 30;99(5):2059-2067. doi: 10.1002/jsfa.9388. Epub 2018 Nov 8.
Following the boom in durum wheat breeding, ancient wheat disappeared from the human diet and old durum wheat varieties were replaced by what is believed to be their better versions: higher yielding modern varieties grown in high-input systems. Breeders have worked intensely ever since to improve the quality of durum wheat traits - mainly gluten subunit alleles - to obtain superior technological quality in the main durum wheat end products (first pasta and then bread) but conflicts about predicting their quality still exist. This is because quality is neither governed by one trait alone nor conditioned by a single controllable factor. This review discusses the evolution of wheat varieties from ancient to old, and then modern durum wheat in terms of agronomy, genetics, technological, and end-product qualities. Environmental effects will not be discussed. Moving from ancient to modern durum wheat varieties, grain yield increased, grain protein concentration decreased, and gluten strength and dough toughness improved, ameliorating the quality of pasta but decreasing the durum wheat versatility. © 2018 Society of Chemical Industry.
17Co-localization of gluten consumption and HLA-DQ2 and -DQ8 genotypes, a clue to the history of celiac disease.PubMed
Elena Lionetti, Carlo Catassi
Dig Liver Dis. 2014 Dec;46(12):1057-63. doi: 10.1016/j.dld.2014.08.002. Epub 2014 Sep 4.
Celiac disease is an immune-mediated disorder triggered by gluten in genetically susceptible persons. Despite its detrimental effects on human health, it has not disappeared over time. The current evolutionary theory is that celiac disease is more common in areas reached later by agricultural revolution than in countries that started consumption of wheat earlier, due to negative selection caused by celiac disease. We reviewed data on worldwide prevalence of celiac disease, wheat consumption, and frequencies of HLA-celiac-disease-predisposing-genotypes to investigate their mutual relationship. Studies assessing prevalence of celiac disease were identified through a MEDLINE search. Wheat consumption and frequencies of HLA-DQ2-DQ8 were obtained from Food and Agriculture Organization of the United Nations and allelefrequencies.net database. Correlations between celiac disease, wheat consumption, and HLA were analyzed by linear regression. We observed a significant correlation between wheat consumption and HLA DQ2 (p=0.01) and the sum of DQ2 and DQ8 (p=0.01) frequencies. Wheat consumption and HLA-DQ2 tend to co-localize in different continents. The correlation between the prevalence of celiac disease and either DQ2 and/or DQ8, or the product of DQ2+DQ8*wheat consumption was not statistically significant. Co-localization of gluten consumption and HLA-celiac-disease-predisposing-genotypes can be explained by positive selection of HLA-DQ2 genes in wheat-consuming areas, and "demic diffusion" of Middle East farmers into Europe.
18Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder.PubMed
Margaret R Dunne, Greg Byrne, Fernando G Chirdo, et al.
Front Immunol. 2020 Jul 8;11:1374. doi: 10.3389/fimmu.2020.01374. eCollection 2020.
Coeliac disease is a common small bowel enteropathy arising in genetically predisposed individuals and caused by ingestion of gluten in the diet. Great advances have been made in understanding the role of the adaptive immune system in response to gluten peptides. Despite detailed knowledge of these adaptive immune mechanisms, the complete series of pathogenic events responsible for development of the tissue lesion remains less certain. This review contributes to the field by discussing additional mechanisms which may also contribute to pathogenesis. These include the production of cytokines such as interleukin-15 by intestinal epithelial cells and local antigen presenting cells as a pivotal event in the disease process. A subset of unconventional T cells called gamma/delta T cells are also persistently expanded in the coeliac disease (CD) small intestinal epithelium and recent analysis has shown that these cells contribute to pathogenic inflammation. Other unconventional T cell subsets may play a local immunoregulatory role and require further study. It has also been suggested that, in addition to activation of pathogenic T helper cells by gluten peptides, other peptides may directly interact with the intestinal mucosa, further contributing to the disease process. We also discuss how myofibroblasts, a major source of tissue transglutaminase and metalloproteases, may play a key role in intestinal tissue remodeling. Contribution of each of these factors to pathogenesis is discussed to enhance our view of this complex disorder and to contribute to a wider understanding of chronic immune-mediated disease.
19Coeliac disease.PubMed
Benjamin Lebwohl, David S Sanders, Peter H R Green
Lancet. 2018 Jan 6;391(10115):70-81. doi: 10.1016/S0140-6736(17)31796-8. Epub 2017 Jul 28.
Coeliac disease occurs in about 1% of people in most populations. Diagnosis rates are increasing, and this seems to be due to a true rise in incidence rather than increased awareness and detection. Coeliac disease develops in genetically susceptible individuals who, in response to unknown environmental factors, develop an immune response that is subsequently triggered by the ingestion of gluten. The disease has many clinical manifestations, ranging from severe malabsorption to minimally symptomatic or non-symptomatic presentations. Diagnosis requires the presence of duodenal villous atrophy, and most patients have circulating antibodies against tissue transglutaminase; in children, European guidelines allow a diagnosis without a duodenal biopsy provided that strict symptomatic and serological criteria are met. Although a gluten-free diet is an effective treatment in most individuals, a substantial minority develop persistent or recurrent symptoms. Difficulties adhering to a gluten-free diet have led to the development of non-dietary therapies, several of which are undergoing trials in human beings.
20Celiac Disease: Fallacies and Facts.PubMed
Jocelyn A Silvester, Amelie Therrien, Ciaran P Kelly
Am J Gastroenterol. 2021 Jun 1;116(6):1148-1155. doi: 10.14309/ajg.0000000000001218.
Our understanding of the pathophysiology of celiac disease has progressed greatly over the past 25 years; however, some fallacies about the clinical characteristics and management persist. Worldwide epidemiologic data are now available showing that celiac disease is ubiquitous. An elevated body mass index is common at the time of the diagnosis. The gluten-free diet (GFD) is an imperfect treatment for celiac disease; not all individuals show a response. This diet is widely used by people without celiac disease, and symptomatic improvement on a GFD is not sufficient for diagnosis. Finally, the GFD is burdensome, difficult to achieve, and thus has an incomplete efficacy, opening exciting opportunities for novel, nondietary treatments.
21Epidemiology, Presentation, and Diagnosis of Celiac Disease.PubMed
Benjamin Lebwohl, Alberto Rubio-Tapia
Gastroenterology. 2021 Jan;160(1):63-75. doi: 10.1053/j.gastro.2020.06.098. Epub 2020 Sep 18.
The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. If proven accurate and scalable, assays that detect gluten-HLA tetramer complexes might be used in diagnosis to be made in the context of a gluten-free diet without intestinal biopsy.
22Celiac Disease-Related Conditions: Who to Test?PubMed
Fabiana Zingone, Julio C Bai, Christophe Cellier, et al.
Gastroenterology. 2024 Jun;167(1):64-78. doi: 10.1053/j.gastro.2024.02.044. Epub 2024 Mar 7.
Celiac disease (CeD) is a chronic immune-mediated condition triggered by gluten consumption in genetically predisposed individuals. Approximately 1% of the general population is affected by the disorder. Disease presentation is heterogeneous and, despite growing awareness among physicians and the public, it continues to be underestimated. The most effective strategy for identifying undiagnosed CeD is proactive case finding through serologic testing in high-risk groups. We reviewed the most recent evidence on the association between CeD and more than 20 conditions. In light of this review, CeD screening is recommended in individuals with (1) autoimmune disease and accompanying symptoms suggestive of CeD; (2) diseases that may mimic CeD (eg, irritable bowel syndrome [IBS], inflammatory bowel disease [IBD], and microscopic colitis); and (3) among patients with conditions with a high CeD prevalence: first-degree relatives, idiopathic pancreatitis, unexplained liver enzyme abnormalities, autoimmune hepatitis, primary biliary cholangitis, hyposplenism or functional asplenia with severe bacterial infection, type 1 diabetes mellitus, Hashimoto's thyroiditis and Graves' disease, Sjögren's syndrome, dermatitis herpetiformis, recurrent aphthous syndrome and enamel defects, unexplained ataxia, peripheral neuropathy, delayed menarche or premature menopause, Down syndrome, Turner syndrome, Williams syndrome, chronic fatigue syndrome, IgA nephropathy, and IgA deficiency. CeD serology should be the initial step in the screening process. However, for patients with any of the aforementioned disorders who are undergoing upper endoscopy, biopsies should be performed to rule out CeD.
23Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects.PubMed
Taoufik Ben Houmich, Brahim Admou
Int J Immunopathol Pharmacol. 2021 Jan-Dec;35:20587384211008709. doi: 10.1177/20587384211008709.
Celiac disease (CD) is characterized by clinical polymorphism, with classic, asymptomatic or oligosymptomatic, and extra-intestinal forms, which may lead to diagnostic delay and exposure to serious complications. CD is a multidisciplinary health concern involving general medicine, pediatric, and adult gastroenterology, among other disciplines. Immunology and pathology laboratories have a fundamental role in diagnosing and monitoring CD. The diagnosis consists of serological testing based on IgA anti-transglutaminase (TG2) antibodies combined with IgA quantification to rule out IgA deficiency, a potential misleading factor of CD diagnosis. Positive TG2 serology should be corroborated by anti-endomysium antibody testing before considering an intestinal biopsy. Owing to multiple differential diagnoses, celiac disease cannot be confirmed based on serological positivity alone, nor on isolated villous atrophy. In children with classical signs or even when asymptomatic, with high levels of CD-linked markers and positive HLA DQ2 and/or DQ8 molecules, the current trend is to confirm the diagnosis on basis of the non-systematic use of the biopsy, which remains obligatory in adults. The main challenge in managing CD is the implementation and compliance with a gluten-free diet (GFD). This explains the key role of the dietitian and the active participation of patients and their families throughout the disease-management process. The presence of the gluten in several forms of medicine requires the sensitization of physicians when prescribing, and particularly when dispensing gluten-containing formulations by pharmacists. This underlines the importance of the contribution of the pharmacist in the care of patients with CD within the framework of close collaboration with physicians and nutritionists.
24Serological testing for celiac disease in children.PubMed
Marleena Repo, Sara Koskimaa, Saana Paavola, et al.
Expert Rev Gastroenterol Hepatol. 2025 Jan-Feb;19(2):155-164. doi: 10.1080/17474124.2025.2462245. Epub 2025 Feb 4.
INTRODUCTION: Celiac disease is one of the most common chronic immune-mediated gastrointestinal conditions, characterized by the presence of disease-specific serum antibodies against self-antigen transglutaminase 2. Even though modern serological assays can identify most untreated celiac disease patients and are also increasingly being used to establish a diagnosis, several challenges are associated with the tests, including a lack of standardization, the variable sensitivity and specificity of commercial assays, and inadequate sensitivity for monitoring adherence to a gluten-free diet. AREAS COVERED: This narrative review outlines the current use of serological tests in case-finding and screening, as well as in the follow-up of dietary treatment. Additionally, the possible challenges and pitfalls of serological tests, along with future directions, are addressed. EXPERT OPINION: The excellent accuracy of modern autoantibody tests, especially for greatly elevated levels of transglutaminase 2 antibodies and positive endomysial antibodies, enables using serological testing in establishing a diagnosis. However, better international standardization of the assays is required, the necessity of endomysial antibody testing needs to be further scrutinized, and additional research is needed to improve noninvasive tools for follow-up and to further expand the no-biopsy criteria for celiac disease.
25Dietary management of celiac disease: Revisiting the guidelines.PubMed
Xenophon Theodoridis, Maria G Grammatikopoulou, Arianna Petalidou, et al.
Nutrition. 2019 Oct;66:70-77. doi: 10.1016/j.nut.2019.04.008. Epub 2019 Apr 26.
OBJECTIVE: Medical nutrition therapy (MNT), by lifelong compliance with a gluten-free diet, is likely the only treatment for celiac disease (CD). Clinical practice guidelines (CPGs) regarding the management of CD emphasize the role of MNT over other treatment options. The aim of the present study was to review and critically appraise CD-specific MNT CPGs and identify areas in need of improvement for better adherence and outcomes. METHODS: A comprehensive search was performed using PubMed, Guidelines International Network (GIN), Google Scholar, gray literature, and websites of CD scientific organizations for CPGs, consensus and practice papers on the dietary management of CD, published in the English language. RESULTS: A total of 12 CPGs were retrieved and critically appraised by three independent reviewers using the Appraisal of Guidelines Research & Evaluation (AGREE) II instrument. All CPGs were of low quality based on AGREE II. Among the 12 CPGs, the National Institute for Health and Care Excellence guidelines achieved the highest score and were unanimously recommended without modifications by the three reviewers, whereas the American Gastroenterology Association, Alberta Health Services, British Society of Paediatric Gastroenterology, Hepatology and Nutrition, Clinical Resource Efficiency Support Team, and Federation of International Societies of Pediatric Gastroenterology, Hepatology and Nutrition guidelines received the lowest scores. CONCLUSIONS: The present study reveals the low quality of guidelines regarding the MNT of CD patients, indicating the need for updated and improved guidelines taking into consideration the proposed items of AGREE II.
26Long-term care for patients with coeliac disease in the UK: a review of the literature and future directions.PubMed
M Kurien, N Trott, D S Sanders
J Hum Nutr Diet. 2016 Oct;29(5):617-23. doi: 10.1111/jhn.12379. Epub 2016 May 16.
Coeliac disease is a common digestive disorder that affects 1% of adults. It is characterised by mucosal damage of the small intestine caused by dietary gluten. The main treatment for coeliac disease is a lifelong gluten-free diet, which can reduce morbidity and mortality and also improve quality of life. Despite the benefits, adhering to this diet is often challenging, with patients often struggling to sustain dietary restriction. Structured follow-up for coeliac disease is recommended in international guidelines for improving adherence and for detecting complications;however, uncertainty exists concerning exactly who should be administering this follow-up care. Here, we undertake a review of the current approaches described in the literature to follow-up patients with coeliac disease, and assess the efficacy of these differing models. We also explore future directions for the care of these patients in the context of the UK National Health Service (a publicly funded healthcare system). Although the focus of this review pertains to follow-up within the UK healthcare system, these problems are recognised to be international, and so the findings of our review are likely to be of interest to all healthcare professionals seeing and managing patients with coeliac disease.
27European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders.PubMed
Abdulbaqi Al-Toma, Umberto Volta, Renata Auricchio, et al.
United European Gastroenterol J. 2019 Jun;7(5):583-613. doi: 10.1177/2050640619844125. Epub 2019 Apr 13.
This guideline presents recommendations for the management of coeliac disease (CD) and other gluten-related disorders both in adults and children. There has been a substantial increase in the prevalence of CD over the last 50 years and many patients remain undiagnosed. Diagnostic testing, including serology and biopsy, should be performed on a gluten-containing diet. The diagnosis of CD is based on a combination of clinical, serological and histopathological data. In a group of children the diagnosis may be made without biopsy if strict criteria are available. The treatment for CD is primarily a gluten-free diet (GFD), which requires significant patient education, motivation and follow-up. Slow-responsiveness occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms necessitate a review of the original diagnosis, exclude alternative diagnoses, confirm dietary adherence (dietary review and serology) and follow-up biopsy. In addition, evaluation to exclude complications of CD, such as refractory CD or lymphoma, should be performed. The guideline also deals with other gluten-related disorders, such as dermatitis herpetiformis, which is a cutaneous manifestation of CD characterized by granular IgA deposits in the dermal papillae. The skin lesions clear with gluten withdrawal. Also, less well-defined conditions such as non-coeliac gluten sensitivity (NCGS) and gluten-sensitive neurological manifestations, such as ataxia, have been addressed. Newer therapeutic modalities for CD are being studied in clinical trials but are not yet approved for use in practice.
28Mesalazine treatment in organotypic culture of celiac patients: Comparative study with gluten free diet.PubMed
Elisabetta Benedetti, Angelo Viscido, Vanessa Castelli, et al.
J Cell Physiol. 2018 Jun;233(6):4383-4390. doi: 10.1002/jcp.26217. Epub 2018 Jan 4.
Given the central role of gluten in the pathogenesis of celiac disease (CD), a strict gluten-free diet (GFD) is the only validated treatment able to restore epithelium integrity and eliminate risks of complications. The risk of gluten contamination and the persistence of inflammation, even in patients strictly adhering to GFD, may render this treatment not always effective claiming the necessity of different new solutions. Oxidative and nitrosative stress have been indicated to play a pathophysiological role in CD. Mesalazine (5-ASA), a drug largely used in inflammatory bowel disease, has potent antinflammatory and antioxidant effects. In fact, mesalazine has been shown to decrease in vitro gluten induced cytokine response and it has been used in vivo in some refractory condition. However, its effect has never compared to that of GFD. The present study aimed to address this issue by comparing the ability of mesalazine and GFD in treating gluten-induced inflammation and oxidative stress. These effects were studied on duodenal mucosa biopsy cultures from newly diagnosed CD patients, treated or not in vitro with mesalazine, and CD biopsy cultures from patients on gluten-free diet for at least one year; and a cohort of controls constituted by healty subjects. On these models, the antioxidant cellular defences, the PPARγ, NF-kB and NOS2 proteins levels were studied. This study shows that mesalazine is as effective as GFD in reducing oxidative burst and inducing PPARγ expression; moreover it resulted more effective than GFD in decreasing NF-kB and NOS2 to the levels of controls.
29Society for the Study of Celiac Disease position statement on gaps and opportunities in coeliac disease.PubMed
M Ines Pinto-Sanchez, Jocelyn A Silvester, Benjamin Lebwohl, et al.
Nat Rev Gastroenterol Hepatol. 2021 Dec;18(12):875-884. doi: 10.1038/s41575-021-00511-8. Epub 2021 Sep 15.
Progress has been made in understanding coeliac disease, a relatively frequent and underappreciated immune-mediated condition that occurs in genetically predisposed individuals. However, several gaps remain in knowledge related to diagnosis and management. The gluten-free diet, currently the only available management, is not curative or universally effective (some adherent patients have ongoing duodenal injury). Unprecedented numbers of emerging therapies, including some with novel tolerogenic mechanisms, are currently being investigated in clinical trials. In March 2020, the Celiac Disease Foundation and the Society for the Study of Celiac Disease convened a consensus workshop to identify high-yield areas of research that should be prioritized. Workshop participants included leading experts in clinical practice, academia, government and pharmaceutical development, as well as representatives from patient support groups in North America. This Roadmap summarizes key advances in the field of coeliac disease and provides information on important discussions from the consensus approach to address gaps and opportunities related to the pathogenesis, diagnosis and management of coeliac disease. The morbidity of coeliac disease is often underestimated, which has led to an unmet need to improve the management of these patients. Expanded research funding is needed as coeliac disease is a potentially curable disease.
30Celiac disease and non-celiac gluten sensitivity.PubMed
Benjamin Lebwohl, Jonas F Ludvigsson, Peter H R Green
BMJ. 2015 Oct 5;351:h4347. doi: 10.1136/bmj.h4347.
Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.
31Non-Celiac Gluten Sensitivity: An Update.PubMed
Feliznando Isidro Cárdenas-Torres, Francisco Cabrera-Chávez, Oscar Gerardo Figueroa-Salcido, et al.
Medicina (Kaunas). 2021 May 24;57(6):526. doi: 10.3390/medicina57060526.
Non-celiac gluten sensitivity (NCGS) is a clinical entity characterized by the absence of celiac disease and wheat allergy in patients that trigger reproducible symptomatic responses to gluten-containing foods consumption. Due to the lack of sensitive and reproducible biomarkers for NCGS diagnosis, placebo-controlled gluten challenges must be carried out for its diagnosis. The gluten challenges can be either double- or single-blind, for research or clinical practice purposes, respectively. For improving our understanding about the magnitude and relevance of NCGS in different populations, epidemiological studies based on self-report have been carried out. However, the gluten challenge-based prevalence of NCGS remains to be estimated. Since NCGS was recently recognized as a clinical entity, more studies are needed to delve into NCGS pathogenesis, for instance, the molecular interactions between the suspected cereal grain components that trigger NCGS, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and amylase and trypsin inhibitors, and the immune system remains to be elucidated. Although still under debate, NCGS patients can be susceptible to only one or more than one of the NCGS triggers. The treatment of NCGS involves the dietary restriction of the suspected triggers of the disease, but there is controversial data about the effectiveness of different dietary interventions such as the gluten-free diet and low-FODMAP diet. Certainly, our understanding of NCGS is improving quickly due to the constant availability of new scientific information on this topic. Thus, the aim of the present narrative review is to present an up-to-date overview on NCGS from epidemiology to current therapy.
32Non-celiac gluten sensitivity: literature review.PubMed
Pasquale Mansueto, Aurelio Seidita, Alberto D'Alcamo, et al.
J Am Coll Nutr. 2014;33(1):39-54. doi: 10.1080/07315724.2014.869996.
BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.
33Nonceliac Gluten Sensitivity.PubMed
Maria Vazquez-Roque, Amy S Oxentenko
Mayo Clin Proc. 2015 Sep;90(9):1272-7. doi: 10.1016/j.mayocp.2015.07.009.
Nonceliac gluten sensitivity (NCGS) is the clinical term used to describe gastrointestinal (GI) and/or extraintestinal symptoms associated with gluten ingestion. The prevalence of NCGS is unknown. The condition has clinical features that overlap with those of celiac disease (CD) and wheat allergy (WA). The pathophysiologic process in NCGS is thought to be through an innate immune mechanism, whereas CD and WA are autoimmune- and allergen-mediated, respectively. However, dietary triggers other than gluten, such as the fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, have been implicated. Currently, no clinical biomarker is available to diagnose NCGS. Exclusion of CD and WA is necessary in the evaluation of a patient suspected to have NCGS. The onset of symptoms in patients with NCGS can occur within hours or days of gluten ingestion. Patients with NCGS have GI and extraintestinal symptoms that typically disappear when gluten-containing grains are eliminated from their diets. However, most patients suspected to have NCGS have already initiated a gluten-free diet at the time of an evaluation. A gluten elimination diet followed by a monitored open challenge of gluten intake to document recurrence of GI and/or extraintestinal symptoms can sometimes be helpful. If NCGS is strongly suggested, then a skilled dietitian with experience in counseling on gluten-free diets can provide proper patient education. Additional research studies are warranted to further our understanding of NCGS, including its pathogenesis and epidemiology, and to identify a biomarker to facilitate diagnosis and patient selection for proper management.
34Non celiac gluten sensitivity and diagnostic challenges.PubMed
Giovanni Casella, Vincenzo Villanacci, Camillo Di Bella, et al.
Gastroenterol Hepatol Bed Bench. 2018 Summer;11(3):197-202.
Non-celiac gluten sensitivity (NCGS), also referred to as non-celiac wheat sensitivity (NCWS), is a clinical syndrome characterized by both intestinal and extra-intestinal symptoms responsive to the withdrawal of gluten-containing food from the diet. The aim of this review is to summarize recent advances in research and provide a brief overview of the history of the condition for the benefit of professionals working in gastroenterology. Academic databases such as PubMed and Google Scholar were searched using key words such as "non-celiac gluten sensitivity", "gluten related disorders", and the studies outlined in reference page were selected and analysed. Most of the analysed studiers agree that NCGS would need to be diagnosed only after exclusion of celiac disease and wheat allergy, and that a reliable serological marker is not available presently. The mechanisms causing symptoms in NCGS after gluten ingestion are largely unknown, but recent advances have begun to offer novel insights. The estimated prevalence of NCGS, at present, varies between 0.6 and 6%. There is an overlap between irritable bowel syndrome and NCGS with regard to the similarity of gastrointestinal symptoms. The histologic characteristics of NCGS are still under investigation, ranging from normal histology to slight increase in the number of T lymphocytes in the superficial epithelium of villi. Positive response to gluten free diet for a limited period (e.g., 6 weeks), followed by the reappearance of symptoms after gluten challenge appears, at this moment, to be the best approach for confirming diagnosis. The Salerno expert criteria may help to diagnose NCGS accurately in particular for research purposes but it has limited applicability in clinical practice.
35Non-coeliac gluten sensitivity.PubMed
Peter R Gibson, Gry I Skodje, Knut E A Lundin
J Gastroenterol Hepatol. 2017 Mar;32 Suppl 1:86-89. doi: 10.1111/jgh.13705.
Irritable bowel syndrome-like symptoms in response to wheat ingestion is common and well described, but whether the reaction is due to gluten (i.e., non-coeliac gluten sensitivity), other wheat proteins, or FODMAPs (mostly fructans) alone or in combinations has not been clearly defined. Exclusion of coeliac disease in the presence of negative serology, and normal villous architecture but increased density of intraepithelial lymphocytes on duodenal biopsies, is difficult. Furthermore, the confidence by which a positive diagnosis is made or non-coeliac gluten sensitivity is excluded by blinded placebo-controlled rechallenge with wheat protein is reduced by strong nocebo responses generally found in patients with self-reported non-coeliac gluten sensitivity. The absence of a clear biological mechanism of action and difficulties with the design and interpretation of research studies have plunged this entity into even deeper controversy. In the absence of clarity in its diagnosis, the epidemiology, prognosis, and therapeutic approaches to a patient who may be gluten sensitive remain to be determined. Adequate understanding of the issues surrounding the controversy and further research will slowly unravel the truth behind the problem.
36Self-reported Non-celiac Gluten Sensitivity in the Korean Population: Demographic and Clinical Characteristics.PubMed
Ra Ri Cha, Jeong Hwan Kim, Hoon Sup Koo, et al.
J Neurogastroenterol Motil. 2022 Apr 30;28(2):283-290. doi: 10.5056/jnm21108.
BACKGROUND/AIMS: Non-celiac gluten sensitivity is characterized by intestinal and extra intestinal symptoms associated with the consumption of gluten-containing food. Since biomarkers for non-celiac gluten sensitivity are lacking, its prevalence is estimated based on self-reported symptoms. However, no data exist on self-reported non-celiac gluten sensitivity in the Korean population. Thus, we aim to investigate the prevalence of self-reported non-celiac gluten sensitivity in the Korean population and to determine its demographic and clinical characteristics. METHODS: This study surveyed Korean participants aged 18-80 years who visited gastroenterology outpatient clinics at 9 tertiary hospitals in South Korea from January 2016 to February 2017. They were questioned regarding symptoms related to gluten ingestion: degree of discomfort (visual analog scale score), frequency, time of symptom onset, and duration. Abdominal discomfort caused by 11 different kinds of gluten-containing Korean food items was investigated. RESULTS: More non-celiac gluten sensitivity self-reporters were identified among those with irritable bowel syndrome (33.6%) than among controls (5.8%). Major gastrointestinal symptoms included bloating (75.0%), abdominal discomfort (71.3%), and belching (45.0%). Common extra-intestinal symptoms included fatigue (20.0%) and headache (13.7%). More than half of those who self-reported non-celiac gluten sensitivity (66.3%) developed symptoms within 1 hour of food ingestion, and symptoms were localized in the upper abdomen (37.5%) and entire abdomen (30.0%). CONCLUSION: Our findings suggest that if there are gluten-related symptoms in irritable bowel syndrome, the possibility of accompanying non-celiac gluten sensitivity should be considered.
37Recent advances in understanding non-celiac gluten sensitivity.PubMed
Maria Raffaella Barbaro, Cesare Cremon, Vincenzo Stanghellini, et al.
F1000Res. 2018 Oct 11;7. doi: 10.12688/f1000research.15849.1. eCollection 2018.
Non-celiac gluten sensitivity (NCGS) is a condition characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing foods in the absence of celiac disease and wheat allergy. The diagnosis is cumbersome and currently confirmed only by gluten withdrawal and double-blind placebo challenge protocols. There is great overlap in symptoms between NCGS and other functional gastrointestinal disorders, making a differential diagnosis difficult. The pathophysiology of NCGS is largely unclear, and there are contrasting data on the trigger of this condition. This review will highlight the state-of-the-art knowledge on NCGS and the key open questions.
38Non-celiac gluten sensitivity: Clinical presentation, etiology and differential diagnosis.PubMed
Marta Expósito Miranda, Luz García-Valdés, Elena Espigares-Rodríguez, et al.
Gastroenterol Hepatol. 2023 Aug-Sep;46(7):562-571. doi: 10.1016/j.gastrohep.2022.10.001. Epub 2022 Oct 13.
Non-celiac gluten sensitivity (NCGS) is the latest pathology incorporated into the group of gluten-related disorders. This review addresses the evidence on its etiology, differential diagnosis and symptomatology. Although NCGS is defined by a reaction to gluten, other possible etiopathogenic mechanisms have been described, such as an inadequate response to other components of wheat or to FODMAPs, with the term non-celiac sensitivity to wheat recently being extended. There are contradictory results on the validity of the diagnostic protocol of the Salerno experts. Evidence on diagnostic biomarkers for NCGS is scarce, although some studies indicate the following: antigliadin antibodies, zonulin, ALCAT test, micro-RNA, incRNA and certain cytokines. In NCGS, abdominal pain and fatigue are the most common symptoms. In addition, altered nutritional status is common. In conclusion, more research on NCGS is needed to improve understanding of its etiopathogenesis and clinical features.
39Nonceliac Gluten and Wheat Sensitivity.PubMed
Anam Khan, Milena Gould Suarez, Joseph A Murray
Clin Gastroenterol Hepatol. 2020 Aug;18(9):1913-1922.e1. doi: 10.1016/j.cgh.2019.04.009. Epub 2019 Apr 10.
Non-celiac gluten and/or wheat sensitivity (NCGS) is thought to be an immune-mediated reaction to gluten or other components of wheat (eg, fructans or amylase trypsin inhibitors) with intestinal and extraintestinal symptoms which improve once gluten and/or wheat is eliminated from the diet and after a diagnosis of celiac disease and wheat allergy have been excluded with appropriate testing. However, there is a great deal of skepticism within the scientific community questioning the existence of NCGS as a distinct clinical disorder. There are no strict diagnostic criteria and a placebo-controlled rechallenge trial has been recommended for diagnosis. In research settings, a double-blind placebo-controlled rechallenge trial has been recommended for diagnosis. There are limited studies estimating the prevalence of NCGS using this study design. The existing studies have variable results likely due to the lack of a uniform diagnostic criterion, a great deal of dependence on the patient's perception of symptoms and a large nocebo effect in existing studies. In clinical practice, a single blind placebo-controlled rechallenge trial has been recommended for diagnosis. The pathogenesis of NCGS is unclear and there is no known biomarker or diagnostic histologic lesion for this condition. It is important to adopt a multidisciplinary team approach to patients with suspected NCGS with involvement of the primary care doctor, gastroenterologist, pathologist and nutritionist who may play an important role in diagnosis and treatment. There may especially be a role in elimination of food containing high quantity of both gluten and fructans. Furthermore, patients should be educated on the nutritional implications of consuming a long-term gluten-free diet.
40Gluten Vehicle and Placebo for Non-Celiac Gluten Sensitivity Assessment.PubMed
Oscar Gerardo Figueroa-Salcido, Noé Ontiveros, Francisco Cabrera-Chavez
Medicina (Kaunas). 2019 Apr 26;55(5):117. doi: 10.3390/medicina55050117.
Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by gastrointestinal and extraintestinal manifestations triggered after gluten ingestion in the absence of celiac disease and wheat allergy. Because of the lack of biomarkers for NCGS diagnosis, the cornerstone for its assessment is a single- or double-blind placebo-controlled (DBPC) gluten challenge. However, there are some non-standardized points in the diagnostic approach proposed by the experts. This complicate comparisons among the results published by different research groups. The gluten vehicle and placebo must be indistinguishable from each other, which entails sensory and technological evaluations of the designed gluten vehicle and placebo products. At the moment, there is no standardized method for the preparation of the gluten vehicle and placebo for carrying out DBPC gluten challenges for NCGS assessment. This review focuses on the challenges that researchers have to face, either for the development of an accepted gluten vehicle and placebo or for identifying NCGS cases on the basis of DBPC gluten challenges.
41Pathophysiology of non-celiac gluten sensitivity: where are we now?PubMed
Giacomo Caio, Gabriele Riegler, Marta Patturelli, et al.
Minerva Gastroenterol Dietol. 2017 Mar;63(1):16-21. doi: 10.23736/S1121-421X.16.02346-1. Epub 2016 Nov 3.
Non-celiac gluten sensitivity (NCGS) is the term used to describe individuals complaining of intestinal and extra-intestinal symptoms related to gluten ingestion and rapidly improving after its withdrawal, and in which both celiac disease (CD) and wheat allergy (WA) were properly ruled out. The prevalence of this condition remains unknown and a lot of questions about the possible pathogenetic mechanisms are still unclarified. It is believed that NCGS represents a heterogeneous condition with different subgroups potentially characterized by different pathogenesis, clinical history, and clinical course. Moreover, a possible overlap with irritable bowel syndrome (IBS) and other functional diseases could complicate patient selection for clinical studies, slowing down the understanding of this disorder. Last but not least, the lack of validated biomarkers remains a significant limitation in research studies on NCGS. Hence, there is a need for strict diagnostic criteria for NCGS.
42Noncoeliac wheat sensitivity and diet.PubMed
Dorota Mańkowska-Wierzbicka, Marta Stelmach-Mardas
Curr Opin Clin Nutr Metab Care. 2020 Sep;23(5):322-327. doi: 10.1097/MCO.0000000000000671.
PURPOSE OF REVIEW: Noncoeliac gluten sensitivity (NCGS) can be suspected after exclusion of coeliac disease and wheat allergy. However, poorly understood pathogenesis of the NCGS, lack of gold standard for diagnosis and agreement in the definition for the NCGS condition, open the space for future investigation. This review aims to give an overview on the diagnosis and effective diet composition in the treatment of NCGS symptoms. RECENT FINDINGS: It appears that a diet low in fermentable oligo, di, and monosaccharides and polyols (FODMAPs) and gluten-free diet play a prominent role in the strategy of NCGS management. Considering available evidence with respect to diagnostic tools, it is challenging to prepare a standard guideline for NCGS diagnosis and treatment with clear cut-offs for symptom reduction/improvement that could directly be translated into test results. Nutritional support, including the use of pre/probiotics, has to be tailored to the individual situation of NCGS patients. SUMMARY: The exclusion of such components of wheat as amylase/trypsin inhibitors, wheat-germ agglutinins, or free of FODMAPs diet can reduce clinical symptoms of NCGS. The further investigation on microbiota changes may strengthen the knowledge in this area, where the major challenge is to develop biomarkers for NCGS investigation.
43Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria.PubMed
Carlo Catassi, Luca Elli, Bruno Bonaz, et al.
Nutrients. 2015 Jun 18;7(6):4966-77. doi: 10.3390/nu7064966.
Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts' recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.
44The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study.PubMed
Marlijne C G de Graaf, Clare L Lawton, Fiona Croden, et al.
Lancet Gastroenterol Hepatol. 2024 Feb;9(2):110-123. doi: 10.1016/S2468-1253(23)00317-5. Epub 2023 Nov 28.
BACKGROUND: Many individuals without coeliac disease or wheat allergy reduce their gluten intake because they believe that gluten causes their gastrointestinal symptoms. Symptoms could be affected by negative expectancy. Therefore, we aimed to investigate the effects of expectancy versus actual gluten intake on symptoms in people with non-coeliac gluten sensitivity (NCGS). METHODS: This randomised, double-blind, placebo-controlled, international, multicentre study was done at the University of Leeds (Leeds, UK), Maastricht University (Maastricht, the Netherlands), and Wageningen University and Research (Wageningen, the Netherlands). People aged 18-70 years with self-reported NCGS (ie, gastrointestinal symptoms within 8 h of gluten consumption) without coeliac disease and wheat allergy were recruited. Participants had to follow a gluten-free or gluten-restricted diet for at least 1 week before (and throughout) study participation and had to be asymptomatic or mildly symptomatic (overall gastrointestinal symptom score ≤30 mm on the Visual Analogue Scale [VAS]) while on the diet. Participants were randomly assigned (1:1:1:1; blocks of eight; stratified by site and gender) to one of four groups based on the expectation to consume gluten-containing (E) or gluten-free (E) oat bread for breakfast and lunch (two slices each) and actual intake of gluten-containing (G) or gluten-free (G) oat bread. Participants, investigators, and those assessing outcomes were masked to the actual gluten assignment, and participants were also masked to the expectancy part of the study. The primary outcome was overall gastrointestinal symptom score on the VAS, which was measured at and corrected for baseline (before breakfast) and hourly for 8 h, with lunch served after 4 h, and analysed per-protocol. Safety analysis included all participants incorporated in the per-protocol analysis. The study is registered at ClinicalTrials.gov, NCT05779358, and has ended. FINDINGS: Between Oct 19, 2018, and Feb 14, 2022, 165 people were screened and 84 were randomly assigned to EG (n=21), EG (n=21), EG (n=20), or EG (n=22). One person in the EG group was excluded due to not following test day instructions, leaving 83 participants in the per-protocol analysis. Median age was 27·0 years (IQR 21·0-45·0), 71 (86%) of 83 people were women, and 12 (14%) were men. Mean overall gastrointestinal symptom score was significantly higher for EG (16·6 mm [95% CI 13·1 to 20·0]) than for EG (6·9 mm [3·5 to 10·4]; difference 9·6 mm [95% CI 3·0 to 16·2], p=0·0010) and EG (7·4 mm [4·2 to 10·7]; difference 9·1 mm [2·7 to 15·6], p=0·0016), but not for EG (11·7 mm [8·3 to 15·1]; difference 4·9 mm [-1·7 to 11·5], p=0·28). There was no difference between EG and EG (difference 4·7 mm [-1·8 to 11·3], p=0·33), EG and EG (difference 4·2 mm [-2·2 to 10·7], p=0·47), and EG and EG (difference -0·5 mm [-7·0 to 5·9], p=1·0). Adverse events were reported by two participants in the EG group (itching jaw [n=1]; feeling lightheaded and stomach rumbling [n=1]) and one participant in the EG group (vomiting). INTERPRETATION: The combination of expectancy and actual gluten intake had the largest effect on gastrointestinal symptoms, reflecting a nocebo effect, although an additional effect of gluten cannot be ruled out. Our results necessitate further research into the possible involvement of the gut-brain interaction in NCGS. FUNDING: Government of the Netherlands Topsector Agri & Food Top Consortium for Knowledge and Innovation, AB Mauri Global Bakery Ingredients, Baking Industry Research Trust, Borgesius-Albert Heijn, CSM Innovation Centre, the International Maize and Wheat Improvement Center (CIMMYT), DSM Food Specialties, Fazer, Healthgrain Forum, the International Association for Cereal Science and Technology, the International Wheat Gluten Association, Lantmännen, Mondelez International, Nederlands Bakkerij Centrum, Nutrition & Santé, Puratos, Rademaker, Sonneveld Group, and Zeelandia HJ Doeleman.
45Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders.PubMed
Maria Raffaella Barbaro, Cesare Cremon, Diana Wrona, et al.
Nutrients. 2020 Dec 4;12(12):3735. doi: 10.3390/nu12123735.
Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut-brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut-brain interaction.
46Sensitivity to wheat, gluten and FODMAPs in IBS: facts or fiction?PubMed
Roberto De Giorgio, Umberto Volta, Peter R Gibson
Gut. 2016 Jan;65(1):169-78. doi: 10.1136/gutjnl-2015-309757. Epub 2015 Jun 15.
IBS is one of the most common types of functional bowel disorder. Increasing attention has been paid to the causative role of food in IBS. Food ingestion precipitates or exacerbates symptoms, such as abdominal pain and bloating in patients with IBS through different hypothesised mechanisms including immune and mast cell activation, mechanoreceptor stimulation and chemosensory activation. Wheat is regarded as one of the most relevant IBS triggers, although which component(s) of this cereal is/are involved remain(s) unknown. Gluten, other wheat proteins, for example, amylase-trypsin inhibitors, and fructans (the latter belonging to fermentable oligo-di-mono-saccharides and polyols (FODMAPs)), have been identified as possible factors for symptom generation/exacerbation. This uncertainty on the true culprit(s) opened a scenario of semantic definitions favoured by the discordant results of double-blind placebo-controlled trials, which have generated various terms ranging from non-coeliac gluten sensitivity to the broader one of non-coeliac wheat or wheat protein sensitivity or, even, FODMAP sensitivity. The role of FODMAPs in eliciting the clinical picture of IBS goes further since these short-chain carbohydrates are found in many other dietary components, including vegetables and fruits. In this review, we assessed current literature in order to unravel whether gluten/wheat/FODMAP sensitivity represent 'facts' and not 'fiction' in IBS symptoms. This knowledge is expected to promote standardisation in dietary strategies (gluten/wheat-free and low FODMAP) as effective measures for the management of IBS symptoms.
47Nonceliac gluten sensitivity.PubMed
Carlo Catassi, Giulia Catassi, Loris Naspi
Curr Opin Clin Nutr Metab Care. 2023 Sep 1;26(5):490-494. doi: 10.1097/MCO.0000000000000925. Epub 2023 Feb 15.
PURPOSE OF REVIEW: To describe recent advances on nonceliac gluten sensitivity (NCGS), a recently described disorder characterized by variable symptoms and frequent irritable bowel syndrome (IBS)-like manifestations. RECENT FINDINGS: The recent description of disease-triggering wheat components other than gluten, such as fructans and amylase-trypsin inhibitors (ATIs), definitely suggests that nonceliac wheat sensitivity (NCWS) is a better 'umbrella' terminology than NCGS. Self-reported NCWS is very common worldwide, particularly in patients seen at the gastroenterology clinic, but many of these diagnoses are not confirmed by standard clinical criteria. A biomarker of NCWS is still lacking, however, subtle histological features at the small intestinal biopsy may facilitate diagnosis. Treatment of NCWS is based on the gluten-free diet (GFD). The GFD has proven to be an effective treatment of a significant proportion of NCWS-related IBS patients. Dietary therapies for IBS, including the GFD, should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Pioneer studies are under way to test the therapeutic efficacy of supplemental gluten-digesting enzyme preparations in patients with NCWS. SUMMARY: Recent studies highlight interesting pathophysiological and clinical features of NCWS. Many questions remain, however, unanswered, such as the epidemiology, a biomarker(s), and the natural history of this clinical entity.
48Gluten-free diet in non-celiac patients: beliefs, truths, advantages and disadvantages.PubMed
Beniamino Palmieri, Maria Vadala', Carmen Laurino
Minerva Gastroenterol Dietol. 2019 Jun;65(2):153-162. doi: 10.23736/S1121-421X.18.02519-9. Epub 2018 Dec 14.
A gluten-free diet is the safest treatment for the treatment of patient with celiac disease (CD) and other gluten-related disorders. However, in the last years, gluten-free diet is one of the most popular diet followed by the general population and by patients affected from others clinical conditions, such as non-celiac gluten sensitivity (NCGS), irritable bowel syndrome (IBS), autism, neurological, psychiatric and rheumatologic diseases and for improving sports practice. This review highlights some questions about the appropriateness of following this trend answering to some questions such as how safe are the current gluten-free products, what are the benefits and side effects of gluten-free diet and what are clinical conditions that might benefit from gluten avoidance.
49Nutritional Imbalances in Adult Celiac Patients Following a Gluten-Free Diet.PubMed
Aner Cardo, Itziar Churruca, Arrate Lasa, et al.
Nutrients. 2021 Aug 21;13(8):2877. doi: 10.3390/nu13082877.
Celiac disease (CD) is a chronic autoimmune disorder of the small intestine, whose only effective treatment is a gluten-free diet (GFD). It is characterized by the atrophy of the intestinal villi that leads to altered nutrient absorption. This study describes the nutritional imbalances which may be found in adults with CD following a GFD. During the first year of treatment, deficiencies will overcome as the intestinal mucosa recovers. Thus, biochemical data will show this progression, together with the decrease in symptoms. In contrast, in the long term, when a strict GFD is followed and mucosal recovery is achieved, analyzing nutrient intake makes more sense. Macronutrient consumption is characterized by its low complex carbohydrate and fiber intakes, and high fat (especially SFA) and sugar intakes. This profile has been related to the consumption of GFP and their nutritional composition, in addition to unbalanced dietary habits. The most notable deficiencies in micronutrients are usually those of iron, calcium and magnesium and vitamin D, E and some of group B. It is necessary to follow up patients with CD and to promote nutritional education among them, since it could help not only to achieve a gluten free but also a balanced diet.
50Celiac disease: understanding the gluten-free diet.PubMed
Karla A Bascuñán, María Catalina Vespa, Magdalena Araya
Eur J Nutr. 2017 Mar;56(2):449-459. doi: 10.1007/s00394-016-1238-5. Epub 2016 Jun 22.
PURPOSE: The only effective and safe treatment of celiac disease (CD) continues being strict exclusion of gluten for life, the so-called gluten-free diet (GFD). Although this treatment is highly successful, following strict GFD poses difficulties to patients in family, social and working contexts, deteriorating his/her quality of life. We aimed to review main characteristics of GFD with special emphasis on factors that may interfere with adherence to it. METHODS: We conducted a search of various databases, such as PubMed, Google Scholar, Embase, and Scielo, with focus on key words such as "gluten-free diet", "celiac disease", "gluten" and "gluten-free diet adherence". Available literature has not reached definitive conclusions on the exact amount of gluten that is harmless to celiac patients, although international agreements establish cutoff points for gluten-free products and advise the use of clinical assessment to tailor the diet according to individual needs. Following GFD must include eliminating gluten as ingredient as well as hidden component and potential cross contamination in foods. There are numerous grains to substitute wheat but composition of most gluten-free products tends to include only a small number of them, especially rice. The diet must be not only free of gluten but also healthy to avoid nutrient, vitamins and minerals deficiencies or excess. Overweight/obesity frequency has increased among celiac patients so weight gain deserves attention during follow up. Nutritional education by a trained nutritionist is of great relevance to achieve long-term satisfactory health status and good compliance. CONCLUSIONS: A balanced GFD should be based on a combination of naturally gluten-free foods and certified processed gluten-free products. How to measure and improve adherence to GFD is still controversial and deserves further study.
51Gluten-Free Diet and Metabolic Syndrome: Could Be a Not Benevolent Encounter?PubMed
Giuseppe Defeudis, Maria Chiara Massari, Giovanni Terrana, et al.
Nutrients. 2023 Jan 26;15(3):627. doi: 10.3390/nu15030627.
Celiac disease is a rising disorder and is becoming frequently diagnosed in recent years. To date, the only available treatment is the gluten-free diet (GFD). The role of gluten on components of metabolic syndrome and on related inflammatory response is still unclear due to controversial results. In recent years, scientific focus on this topic has been growing up, in particular regarding the role of the GFD on glycometabolic parameters and diabetes. In addition, studies on the remaining components showed discordant results, which was likely due to heterogeneous and large celiac disease populations and to the lack of prospective studies. Furthermore, knowledge about the role of the GFD on inflammatory cytokines and the relationship among vitamin D and celiac disease, metabolic syndrome (MS) and GFD is needed. In this narrative review, we provided evidence regarding the role of the GFD on glycometabolic parameters, cholesterol, triglycerides, waist circumference, blood pressure and inflammatory cascade, also evaluating the role of vitamin D, trying to summarize whether this nutritional pattern may be a value-added for subjects with dysmetabolic conditions. Finally, due to the limited findings and very low-certainty evidence, predominantly based on observational studies, the real effects of a GFD on different components of MS, however, are unclear; nevertheless, an improvement in HDL levels has been reported, although data on glycemic levels are discordant.
52Multidimensional Disadvantages of a Gluten-Free Diet in Celiac Disease: A Narrative Review.PubMed
Martyna Marciniak, Aleksandra Szymczak-Tomczak, Dagmara Mahadea, et al.
Nutrients. 2021 Feb 16;13(2):643. doi: 10.3390/nu13020643.
A gluten-free diet is the mainstay method of treatment and the prevention of celiac disease complications. However, an inadequately balanced gluten-free diet can increase the risk of obesity, negatively affect glucose and lipid metabolism, and increase the risk of the metabolic syndrome. Therefore, an adequate nutritional counselling is necessary for patients diagnosed with celiac disease in order to prevent and treat the components of the metabolic syndrome.
53Metabolic syndrome in patients with coeliac disease on a gluten-free diet.PubMed
R Tortora, P Capone, G De Stefano, et al.
Aliment Pharmacol Ther. 2015 Feb;41(4):352-9. doi: 10.1111/apt.13062. Epub 2015 Jan 8.
BACKGROUND: Several studies have shown that weight changes are common in patients with coeliac disease after starting a gluten-free diet (GFD), but data on the prevalence of metabolic syndrome in this population are still scarce. AIMS: To assess the prevalence of metabolic syndrome in patients with CD at diagnosis and 1 year after starting GFD. METHODS: We enrolled all consecutive patients with newly diagnosed coeliac disease (CD) who were referred to our third-level CD Unit. For all patients we collected: waist circumference, BMI, blood pressure, lipid profile (HDL cholesterol, triglycerides) and levels of blood glucose. Diagnosis of metabolic syndrome was made according to the International Diabetes Federation (IDF) criteria for European countries. The prevalence of metabolic syndrome was re-assessed after 12 months of GFD. RESULTS: Ninety-eight patients with CD were assessed, two patients with CD (2%) fulfilled the diagnostic criteria for metabolic syndrome at diagnosis and 29 patients (29.5%) after 12 months of GFD (P < 0.01; OR: 20). With regard to metabolic syndrome sub-categories 1 year after GFD compared to baseline respectively: 72 vs. 48 patients exceeded waist circumference cut-off (P < 0.01; OR: 2.8); 18 vs. 4 patients had high blood pressure (P < 0.01; OR: 5.2); 25 vs. 7 patients exceeded glycemic threshold (P = 0.01; OR: 4.4); 34 vs. 32 patients with CD had reduced levels of HDL cholesterol (P = 0.7); and 16 vs. 7 patients had high levels of triglycerides (P = 0.05). CONCLUSIONS: Patients with coeliac disease show a high risk of metabolic syndrome 1 year after starting a gluten-free diet. We suggest that an in-depth nutritional assessment is undertaken for all patients with coeliac disease.
54The Effect of Gluten Free Diet on Components of Metabolic Syndrome: A Randomized Clinical Trial.PubMed
Mehdi Ehteshami, Rahebeh Shakerhosseini, Fatemeh Sedaghat, et al.
Asian Pac J Cancer Prev. 2018 Oct 26;19(10):2979-2984. doi: 10.22034/APJCP.2018.19.10.2979.
Background: This study aimed to assess the effects of Gluten free diet (GFD) on components of metabolic syndrome (MES). Materials and Methods: In this randomized clinical trial, 50 subjects diagnosed with MES were randomly divided into two groups (n=25). The first group received a GFD and the second group continued their regular diet. Biochemical markers of MES and blood pressure were measured before and after 8-week intervention. Results: Forty five subjects completed the study. A post-hoc comparison of the groups showed no effects of the GFD and control diet on LDL cholesterol, total cholesterol, fasting insulin, HOMA-IR, systolic and diastolic blood pressure levels. The GFD reduced fasting blood glucose, waist circumference (WC) and serum triglyceride concentration significantly compared with the control diet (p<0.05). Conclusion: Short-term GFD reduced WC and improved glycemic control and Triglyceride level in subjects with the metabolic syndrome.
55Gastrointestinal microbiome and gluten in celiac disease.PubMed
Xingxing Wu, Lin Qian, Kexin Liu, et al.
Ann Med. 2021 Dec;53(1):1797-1805. doi: 10.1080/07853890.2021.1990392.
Coeliac disease (CD), also known as gluten sensitive enteropathy, is an autoimmune intestinal disease induced by gluten in genetically susceptible individuals. Gluten is a common ingredient in daily diet and is one of the main environmental factors to induce coeliac disease. Adhering to gluten free diet (GFD) is an effective method for treating CD. Microbiota plays an extremely important role in maintaining human health, and diet is the main factor to regulate the composition and function of gut microbiota. Recent studies have shown that gluten metabolism is closely related to gastrointestinal tract (GIT) microbiota. With the increasing prevalence of coeliac disease, there is a need for alternative treatments to GFD. In this review, biological medication of gluten, relationship between gluten and gut microflora, effect of GFD on GIT microflora, and effect of probiotics on CD were reviewed. By analysing the research progress on relationship between gluten and gastrointestinal microbiome in coeliac disease, this review tried to explore the prospective and potential mechanism of microecological agents in treating coeliac disease.
56Effect of Gluten-Free Diet on Gut Microbiota Composition in Patients with Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity.PubMed
Giacomo Caio, Lisa Lungaro, Nicola Segata, et al.
Nutrients. 2020 Jun 19;12(6):1832. doi: 10.3390/nu12061832.
Celiac disease (CD) and non-celiac gluten/wheat sensitivity (NCG/WS) are the two most frequent conditions belonging to gluten-related disorders (GRDs). Both these diseases are triggered and worsened by gluten proteins ingestion, although other components, such as amylase/trypsin inhibitors (ATI) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), seem to be involved in the NCG/WS onset. Therefore, the only effective treatment to date is the long-life adherence to a strictly gluten-free diet. Recently, increasing attention has been paid to the intestinal barrier, a dynamic system comprising various components, which regulate the delicate crosstalk between metabolic, motor, neuroendocrine and immunological functions. Among the elements characterizing the intestinal barrier, the microbiota plays a key role, modulating the gut integrity maintenance, the immune response and the inflammation process, linked to the CD and NCG/WS outbreak. This narrative review addresses the most recent findings on the gut microbiota modulation induced by the gluten-free diet (GFD) in healthy, CD and NCG/WS patients.
57The Gut Microbiota in Celiac Disease and probiotics.PubMed
Richa Chibbar, Levinus A Dieleman
Nutrients. 2019 Oct 5;11(10):2375. doi: 10.3390/nu11102375.
Celiac disease (CeD) is an immune-mediated enteropathy, and unique in that the specific trigger is known: gluten. The current mainstay of therapy is a gluten-free diet (GFD). As novel therapies are being developed, complementary strategies are also being studied, such as modulation of the gut microbiome. The gut microbiota is involved in the initiation and perpetuation of intestinal inflammation in several chronic diseases. Intestinal dysbiosis has been reported in CeD patients, untreated or treated with GFD, compared to healthy subjects. Several studies have identified differential bacterial populations associated with CeD patients and healthy subjects. However, it is still not clear if intestinal dysbiosis is the cause or effect of CeD. Probiotics have also been considered as a strategy to modulate the gut microbiome to an anti-inflammatory state. However, there is a paucity of data to support their use in treating CeD. Further studies are needed with therapeutic microbial formulations combined with human trials on the use of probiotics to treat CeD by restoring the gut microbiome to an anti-inflammatory state.
58"The Gluten-Free Diet and Its Relationship with Metabolic Syndrome: Dietary Friend or Foe?".PubMed
Vishal Dhruva, Christy Lawson, Caitlin Green, et al.
Curr Nutr Rep. 2021 Dec;10(4):282-287. doi: 10.1007/s13668-021-00371-3. Epub 2021 Sep 12.
PURPOSE OF REVIEW: Celiac disease (CD) is a prevalent digestive illness as well as a budding area of research in the field of gastroenterology. While investigations are underway to find new and improved pharmacological therapies for CD, the gluten-free diet (GFD) remains the only option to effectively manage the condition. RECENT FINDINGS: While the GFD is recommended for patients diagnosed with CD and other gluten-related conditions, studies show the number of individuals on the GFD surpasses the projected number of patients with these medical indications (1). The implications of widespread adoption of this dietary approach are still being determined, with many patients believing this diet will improve overall health and cardiovascular risk. This review analyzes the relationship between a GFD and metabolic syndrome in both non-celiac and celiac patients, concluding that although the diet may slightly improve overall cardiac risk factors, weight, and/or insulin resistance, its use in the absence of a gluten-related disorder is controversial.
59Gluten-free diet on video platforms: Retrospective infodemiology study.PubMed
Chen Ye, Yuehui Fang, Yiyao Lian, et al.
Digit Health. 2024 Jan 15;10:20552076231224594. doi: 10.1177/20552076231224594. eCollection 2024 Jan-Dec.
BACKGROUND: Video platform is an important approach for individuals to access and adopt health information. Online information on gluten-free diet (GFD) videos remains underinvestigated. METHODS: GFD videos were identified by hashtag-based searching strategy. Videos' basic information, engagement metrics, and content were recorded. Mann-Kendall test was performed to examine time trends of submitting videos and engagement metrics. Video quality was evaluated by the DISCERN instrument and the HONcode. RESULTS: A total of 822 videos were included in the analysis, with the majority focusing on gluten-free food recipes. The number of videos related to GFD was showing an upward trend. Engagement metrics varied between platforms and video types, with non-recipe videos receiving higher user engagement. The average DISCERN score was 50.20 out of 80 and the average HONcode score was 1.93 out of 8. Videos submitted by health professionals demonstrated better quality compared to those submitted by patients or general users. CONCLUSION: There was a rise in the number of videos related to GFD on Chinese video platforms. The overall quality of these videos was poor, most of them were not rigorous enough. Highlighting using social media as a health information source has the potential risk of disseminating one-sided messages and misleading. Efforts should be made to enhance the transparency of advertisements and establish clear guidelines for information sharing on social media platforms.
60Twitter Trends for Celiac Disease and the Gluten-Free Diet: Cross-sectional Descriptive Analysis.PubMed
Monique Germone, Casey D Wright, Royce Kimmons, et al.
JMIR Infodemiology. 2022 Dec 5;2(2):e37924. doi: 10.2196/37924. eCollection 2022 Jul-Dec.
BACKGROUND: Few studies have systematically analyzed information regarding chronic medical conditions and available treatments on social media. Celiac disease (CD) is an exemplar of the need to investigate web-based educational sources. CD is an autoimmune condition wherein the ingestion of gluten causes intestinal damage and, if left untreated by a strict gluten-free diet (GFD), can result in significant nutritional deficiencies leading to cancer, bone disease, and death. Adherence to the GFD can be difficult owing to cost and negative stigma, including misinformation about what gluten is and who should avoid it. Given the significant impact that negative stigma and common misunderstandings have on the treatment of CD, this condition was chosen to systematically investigate the scope and nature of sources and information distributed through social media. OBJECTIVE: To address concerns related to educational social media sources, this study explored trends on the social media platform Twitter about CD and the GFD to identify primary influencers and the type of information disseminated by these influencers. METHODS: This cross-sectional study used data mining to collect tweets and users who used the hashtags #celiac and #glutenfree from an 8-month time frame. Tweets were then analyzed to describe who is disseminating information via this platform and the content, source, and frequency of such information. RESULTS: More content was posted for #glutenfree (1501.8 tweets per day) than for #celiac (69 tweets per day). A substantial proportion of the content was produced by a small percentage of contributors (ie, "Superuser"), who could be categorized as self-promotors (eg, bloggers, writers, authors; 13.9% of #glutenfree tweets and 22.7% of #celiac tweets), self-identified female family members (eg, mother; 4.3% of #glutenfree tweets and 8% of #celiac tweets), or commercial entities (eg, restaurants and bakeries). On the other hand, relatively few self-identified scientific, nonprofit, and medical provider users made substantial contributions on Twitter related to the GFD or CD (1% of #glutenfree tweets and 3.1% of #celiac tweets, respectively). CONCLUSIONS: Most material on Twitter was provided by self-promoters, commercial entities, or self-identified female family members, which may not have been supported by current medical and scientific practices. Researchers and medical providers could potentially benefit from contributing more to this space to enhance the web-based resources for patients and families.
61Diet and Psoriasis-Related Information on Instagram: A Quality and Content Analysis of Posts Under Popular Psoriasis Hashtags.PubMed
Sabrina Cowan, Poppy Hawkins, Ghislaine Marks, et al.
J Hum Nutr Diet. 2025 Apr;38(2):e70034. doi: 10.1111/jhn.70034.
BACKGROUND: Psoriasis is a chronic immune-mediated skin condition. Evidence supporting dietary management of psoriasis is limited. However, People Living with Psoriasis (PLwP) trial dietary interventions as a management strategy, often taken from popular literature. Social media is a popular source of nutrition information. However, little is known about the dietary information suggested for psoriasis on these platforms. The aim of this study was to explore the dietary approaches suggested for psoriasis on Instagram and evaluate their quality. METHODOLOGY: Cross-sectional content analysis of Instagram posts providing dietary information for plaque psoriasis management, posted under the 12 most popular psoriasis hashtags. Posts were evaluated for quality using the DISCERN instrument. RESULTS: Overall, 138 Instagram posts were analysed. The most common type of dietary recommendation was 'exclusion', most frequently of alcohol and dairy. Detox and 'clean eating' were also frequently mentioned, as well as the inclusion of protein, and adherence to a gluten-free diet. The most common content creators were those with those with lived experience of psoriasis (29.7%). None of the posts were created by qualified nutrition professionals and only 6.5% were by healthcare professionals (HCPs). The majority (99%) of posts identified were of 'poor' quality. CONCLUSION: Most dietary information on Instagram for managing psoriasis is poor quality, restrictive, unsubstantiated and shared by non-HCPs. Therefore, PLwP may be subject to dietary misinformation when using Instagram. HCPs should be equipped to counter diet and psoriasis misinformation. Further research is needed to investigate appropriate ways to provide dietary support for PLwP.
62Qualitative exploration of the experiences and perceptions of diet in psoriasis management among UK adults.PubMed
Poppy Hawkins, Sarah Mason, Kate Earl, et al.
BMJ Open. 2025 Apr 9;15(4):e085536. doi: 10.1136/bmjopen-2024-085536.
OBJECTIVE: This study aimed to explore the use, experiences and perceptions of diet in psoriasis management among adults with lived experience in the UK. DESIGN: Qualitative. Data were analysed thematically using a reflexive thematic approach. SETTING: Online discussions with adults living with psoriasis in the UK. PARTICIPANTS: Nine adults (two men, seven women) ≥18 years of age, living in the UK, English speaking, with a diagnosis of psoriasis of any severity. RESULTS: Four key themes were generated: (1) impact of diet, (2) dietary modification, (3) dietary information and (4) dietary support. Overall, the majority (n=8) perceived that diet had an impact on their psoriasis. Most participants (n=7) reported trying restrictive diets including dairy free, gluten free and 'cleanses' to help manage their psoriasis with limited success. A perceived lack of dietary support resulted in participants relying on social media and online forums for dietary information. Participants reported a high cognitive burden due to the lack of reliable nutrition guidance and insufficient dietary support from healthcare professionals (HCPs). CONCLUSIONS: Participants rely on social media and online forums for dietary information, which suggest unsubstantiated restrictive diets that could negatively impact health. Participants felt overwhelmed by dietary recommendations and wanted more relevant dietary support. In the absence of evidence-based dietary information for psoriasis, HCPs need to be able to provide basic dietary support and combat misinformation. Larger studies aimed at understanding how best to support people with psoriasis are needed.
63Detection and Quantitation of Gluten in Fermented-Hydrolyzed Foods by Antibody-Based Methods: Challenges, Progress, and a Potential Path Forward.PubMed
Rakhi Panda, Eric A E Garber
Front Nutr. 2019 Jun 28;6:97. doi: 10.3389/fnut.2019.00097. eCollection 2019.
Celiac disease (CD) affects ~1 in 141 individuals in the United States, requiring adherence to a strict gluten-free diet. The Codex Standard and the European Commission states that gluten level of gluten-free foods must not exceed 20 ppm. The FDA requires food bearing the labeling claim "gluten-free" to contain <20 ppm gluten. Accurate quantitation of gluten in fermented-hydrolyzed foods by antibody-based methods is a challenge due to the lack of appropriate reference materials and variable proteolysis. The recent uses of proteases (e.g., proline endopeptidases or PEP) to hydrolyze immunopathogenic sequences of gluten proteins further complicates the quantitation of immunopathogenic gluten. The commercially available antibody-based methods routinely used to detect and quantitate gluten are not able to distinguish between different hydrolytic patterns arising from differences in fermentation processes. This is a severe limitation that makes accurate quantitation and, ultimately, a detailed evaluation of any potential health risk associated with consuming the food difficult. Utilizing gluten-specific antibodies, a recently developed multiplex-competitive ELISA along with western blot analysis provides a potential path forward in this direction. These complimentary antibody-based technologies provide insight into the extent of proteolysis resulting from various fermentation processes and have the potential to aid in the selection of appropriate hydrolytic calibration standards, leading to accurate gluten quantitation in fermented-hydrolyzed foods.
64Balancing consumer protection and scientific integrity in the face of uncertainty: the example of gluten-free foods.PubMed
Margaret Sova McCabe
Food Drug Law J. 2010;65(2):367-90, iii.
In 2009, gluten-free foods were not only "hot" in the marketplace, several countries, including the United States, continued efforts to define gluten-free and appropriate labeling parameters. The regulatory process illuminates how difficult regulations based on safe scientific thresholds can be for regulators, manufacturers and consumers. This article analyzes the gluten-free regulatory landscape, challenges to defining a safe gluten threshold, and how consumers might need more label information beyond the term "gluten-free." The article includes an overview of international gluten-free regulations, the Food and Drug Administration (FDA) rulemaking process, and issues for consumers.
65Comparative analysis of prolamin and glutelin fractions from wheat, rye, and barley with five sandwich ELISA test kits.PubMed
Barbara Lexhaller, Christine Tompos, Katharina Anne Scherf
Anal Bioanal Chem. 2016 Sep;408(22):6093-104. doi: 10.1007/s00216-016-9721-7. Epub 2016 Jun 24.
The safety of gluten-free foods is essential for celiac disease (CD) patients to prevent serious complications. Enzyme-linked immunosorbent assays (ELISAs) are recommended for gluten analysis to monitor the compliance of gluten-free products to the Codex threshold of 20 mg gluten/kg. However, due to the specific features of each gluten ELISA test kit, the results often deviate systematically and largely depend on the characteristics of the antibody. This comprehensive study assessed the specificities and sensitivities of three monoclonal (R5, G12, and Skerritt) and two polyclonal antibodies to the alcohol-soluble prolamin and alcohol-insoluble glutelin fractions of gluten from wheat, rye, and barley, all of which harbor CD-active epitopes. Reversed-phase high-performance liquid chromatography served as independent reference method to quantify gluten protein concentrations and allow comparisons of different gluten fractions within one kit and between kits. Wheat prolamins were detected quite accurately by all antibodies, but high variability between antibody specificities and sensitivities was observed for rye and barley prolamins and rye glutelins, and the largest discrepancies were found for wheat and barley glutelins. The gluten content (sum of prolamins and glutelins) was either overestimated up to six times (rye) or underestimated up to seven times (barley). Overestimation of gluten contents may unnecessarily limit the availability of gluten-free products, but underestimation represents a serious health risk for CD patients. It is important to consider these differences between antibodies used in kits and consider what each kit is capable of measuring, especially with samples where the source of gluten is unknown.
66Gluten Assessment in Beers: Comparison by Different Commercial ELISA Kits and Evaluation of NIR Analysis as a Complementary Technique.PubMed
María Del Pilar Fernández-Gil, Edurne Simon, Anna Gibert, et al.
Foods. 2021 May 23;10(6):1170. doi: 10.3390/foods10061170.
Traditionally, beers are made with gluten-containing cereals. It is crucial to have rapid analytical methodologies that allow gluten content control of the beers for celiac consumers. We assess the content of gluten in 65 conventional and 41 gluten-free labeled beers commercialized in Europe and compare the results in a subgroup of 71 beers with three ELISA kits. This research allows gathering information on the potential complementary utility of NIR analysis applied to gluten analysis of gluten-free beers in terms of time saving. Results obtained with the ELISA technique identified competitive R5 to be the most sensitive in detecting the prolamins, by eliciting a higher number of beers containing gluten above 20 mg/kg. The gluten content in conventional beers tested increased with the presence of wheat as raw material and with the use of ale-type yeasts. By using competitive R5, 3 out of the 41 gluten-free labeled beers appeared to contain gluten above 20 mg/kg, and conversely, 15 out of 65 of the conventional beers showed a gluten content below this threshold. According to our approaches, NIR did not achieve a suitable correlation with ELISA results, neither for gluten quantification nor for discrimination, and therefore, it cannot be proposed as a complementary technique.
67Accuracy of ELISA detection methods for gluten and reference materials: a realistic assessment.PubMed
Carmen Diaz-Amigo, Bert Popping
J Agric Food Chem. 2013 Jun 19;61(24):5681-8. doi: 10.1021/jf3046736. Epub 2013 Jun 6.
The determination of prolamins by ELISA and subsequent conversion of the resulting concentration to gluten content in food appears to be a comparatively simple and straightforward process with which many laboratories have years-long experience. At the end of the process, a value of gluten, expressed in mg/kg or ppm, is obtained. This value often is the basis for the decision if a product can be labeled gluten-free or not. On the basis of currently available scientific information, the accuracy of the obtained values with commonly used commercial ELISA kits has to be questioned. Although recently several multilaboratory studies have been conducted in an attempt to emphasize and ensure the accuracy of the results, data suggest that it was the precision of these assays, not the accuracy, that was confirmed because some of the underlying assumptions for calculating the gluten content lack scientific data support as well as appropriate reference materials for comparison. This paper discusses the issues of gluten determination and quantification with respect to antibody specificity, extraction procedures, reference materials, and their commutability.
68Fundamental study on reactivities of gluten protein types from wheat, rye and barley with five sandwich ELISA test kits.PubMed
Barbara Lexhaller, Christine Tompos, Katharina Anne Scherf
Food Chem. 2017 Dec 15;237:320-330. doi: 10.1016/j.foodchem.2017.05.121. Epub 2017 May 24.
Monitoring the compliance of gluten-free foods to the regulatory threshold of 20mg/kg of gluten is essential for celiac disease patients. The different enzyme-linked immunosorbent assays (ELISAs) for gluten detection each have specific characteristics, but there are only a few systematic comparisons. This fundamental study compared the specificities and sensitivities of the R5, G12 and Skerritt monoclonal and two polyclonal antibodies to well-defined gluten protein types (GPT) isolated from wheat, rye and barley flours. Quantitation of protein concentrations by reversed-phase high-performance liquid chromatography provided independent reference values. The ELISA responses showed high variability depending on the type of cereal, the GPT and the antibody used. Overall, ω1,2-gliadins and γ-75k-secalins were most reactive, whereas ω5-gliadins and γ-, B- and D-hordeins were detected with the lowest sensitivities. These results revealed which GPT each antibody is most sensitive to and provided novel insights that will be helpful for appropriate calibration of ELISAs.
69More than meets the eyes: How can healthiness perceptions and restraint shape the purchase intent of food with nutrition claims?PubMed
Camila de Mello Marsola, Joana Pereira de Carvalho Ferreira, Natalia d'Ottaviano Medina, et al.
Food Res Int. 2025 Feb;203:115910. doi: 10.1016/j.foodres.2025.115910. Epub 2025 Feb 1.
The main goal of this study was to verify relationships between cognitive restraint, priorities in food choice, consumer perceptions, and engagement in slimming process, on willingness to buy foods with nutrition claims (NC). Online questionnaires were answered by 454 consumers over 18 years of age. Cognitive restraint, uncontrolled eating and emotional eating were measured by the Three-Factor Eating Questionnaire-R21. The Eating Motivation Survey was applied to evaluate food choice motives. Consumers' willingness to buy and perceived healthiness were assessed by structured scales. A structural equation model using partial least squares was used to evaluate the impact of different factors on willingness to buy foods with NC. Perceived healthiness impacted positively willingness to buy all foods with NC. Natural concerns had a positive impact on willingness to buy sugar-free chocolate, no sugar added paçoca (peanut sweet), high-protein yoghurt, high-fibre crackers, lactose-free milk and gluten-free bread. Cognitive restraint and engagement in a slimming process positively impacted willingness to buy sugar-free chocolate, high-protein yoghurt, gluten-free bread and light requeijão (Type of cream cheese). Yet, weight control concerns in food choices had a positive impact on willingness to buy light requeijão, high-protein yogurt, no sugar added paçoca and sugar-free chocolate. However, health concerns negatively impacted willingness to buy gluten-free bread, lactose-free milk and high-fibre crackers. The consequences of such perceptions and related factors on food choice and consumption are discussed. The present findings highlight the importance of extending the discussion on food labelling, as well as the careful regulation of the presence of NCs in ultra-processed foods.
70Celiac disease care differs significantly between high- and low-middle-income countries: a global survey of celiac experts from 63 countries.PubMed
Samagra Agarwal, Shubham Prasad, Ashish Agarwal, et al.
J Gastroenterol Hepatol. 2025 Jan;40(1):142-152. doi: 10.1111/jgh.16793. Epub 2024 Nov 11.
BACKGROUND AND AIM: Celiac disease (CeD) is increasingly diagnosed but significant disparities exist in awareness, practices, resources, and legislation worldwide. We conducted a global online survey with CeD experts to assess this disparity internationally. METHODS: A 55 questions survey encompassing nine domains relevant to CeD care (awareness, gluten-free [GF] foods availability/cost/quality, GF labeling, CeD dietician availability, insurance for CeD patients, medical training, research funding, patient support groups, and unmet needs) was generated and sent to CeD experts worldwide electronically. Countries were stratified based on per capita income as high-income (HIC) and lower-income countries (LIC) (including upper-middle-, lower-middle-, and low-income countries). Survey responses were summarized as a single score using principal component analysis. RESULTS: Valid responses were obtained from 131(37.4%) [HIC: 71; LIC: 60] of contacted CeD experts from 63 countries. Compared with HIC, LIC experts perceived worse availability (HIC:80% vs LIC: 47%; P < 0.001), quality (52% vs 20%; P < 0.001), and legislation for labeling of GF foods (82% vs 37%; P < 0.001), with unfavorable reimbursement policies (27% vs 12%; P = 0.002), subsidies (32% vs 13%; P < 0.001), and insurance (76% vs 43%; P < 0.001) for CeD patients. LIC also lacked awareness about CeD among general physicians (69% vs 32%; P < 0.001), trained celiac dieticians (39% vs 12%; P = 0.002), and active CeD patient support groups (93% vs 50%; P < 0.001). All experts believed that GF foods were costly (94% vs 87%), frequently contaminated (27% vs 32%), and unfavorably taxed (97% and 93%). The experts agreed on key unmet needs and better research funding. Overall CeD preparedness score (median 58.3 vs 33.0; P < 0.001) was also associated with income. CONCLUSIONS: The present survey highlights the opinion of global experts on the challenges, opportunities, and preparedness related to CeD and differences worldwide by income.
71American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease.PubMed
Alberto Rubio-Tapia, Ivor D Hill, Carol Semrad, et al.
Am J Gastroenterol. 2023 Jan 1;118(1):59-76. doi: 10.14309/ajg.0000000000002075. Epub 2022 Sep 21.
This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis.
72ACG clinical guidelines: diagnosis and management of celiac disease.PubMed
Alberto Rubio-Tapia, Ivor D Hill, Ciarán P Kelly, et al.
Am J Gastroenterol. 2013 May;108(5):656-76; quiz 677. doi: 10.1038/ajg.2013.79. Epub 2013 Apr 23.
This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients.
73ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease.PubMed
Maria Luisa Mearin, Daniel Agardh, Henedina Antunes, et al.
J Pediatr Gastroenterol Nutr. 2022 Sep 1;75(3):369-386. doi: 10.1097/MPG.0000000000003540. Epub 2022 Jun 27.
OBJECTIVES: To gather the current evidence and to offer recommendations for follow-up and management. METHODS: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. RESULTS: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.
74Celiac Disease: An Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guideline.PubMed
Joann M McDermid, M Angie Almond, Kristen M Roberts, et al.
J Acad Nutr Diet. 2023 Dec;123(12):1793-1807.e4. doi: 10.1016/j.jand.2023.07.018. Epub 2023 Jul 25.
Celiac disease is an autoimmune disorder in which the immune system of genetically susceptible individuals elicits a reaction to gluten causing small intestine damage. If left undiagnosed and untreated, the resulting nutrition malabsorption can lead to anemia, bone disease, growth faltering, or other consequences. The condition is lifelong and lacks a cure; the only treatment is lifelong adherence to a gluten-free diet (GFD). This diet is challenging to follow and adversely influences quality of life; however, it is essential to ensure intestinal recovery and prevent future negative health consequences. The Academy of Nutrition and Dietetics convened an expert panel complemented by a celiac disease patient advocate to evaluate evidence for six topics, including medical nutrition therapy; the GFD; oat consumption; micronutrients; pro-/prebiotics; and the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet. This publication outlines the Academy of Nutrition and Dietetics Evidence Analysis Library methods used to complete the systematic review and guideline development, and summarizes the recommendations and supporting evidence. The guidelines affirm that all individuals with celiac disease should follow a GFD (1C, Imperative) that may include gluten-free oats in adults (2D, Conditional). Children should follow a nutritionally adequate GFD that supports healthy growth and development (Consensus, Imperative) and does not unnecessarily restrict gluten-free oats (Consensus, Conditional). The guidelines indicate nutritional care should include routine nutritional assessment (Consensus, Imperative) and medical nutrition therapy (Consensus, Imperative). At this time, the guidelines do not support a recommendation for the addition of the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (2C, Conditional); prebiotic or probiotic supplementation (2D, Conditional); or micronutrient supplementation (in the absence of nutritional deficiency) (Consensus, Conditional). The 2021 Celiac Disease Evidence-Based Nutrition Guideline will assist registered dietitian nutritionists in providing appropriate evidence-based medical nutrition therapy to support people with celiac disease in achieving and maintaining nutritional health and avoiding adverse celiac disease consequences throughout their lives.
75Gluten Sensitivity.PubMed
Carlo Catassi
Ann Nutr Metab. 2015;67 Suppl 2:16-26. doi: 10.1159/000440990. Epub 2015 Nov 26.
Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on establishing a clear-cut cause-effect relationship between the ingestion of gluten and the appearance of symptoms by a standardized double-blind, placebo-controlled gluten challenge.
76Clinical application of dietary therapies in irritable bowel syndrome.PubMed
Anupam Rej, Amanda Avery, Alexander Charles Ford, et al.
J Gastrointestin Liver Dis. 2018 Sep;27(3):307-316. doi: 10.15403/jgld.2014.1121.273.avy.
BACKGROUND AND AIMS: Diet appears to play a pivotal role in symptom generation in Irritable Bowel Syndrome (IBS). First line dietary therapy for IBS has focused on advice concerning healthy eating and lifestyle management. Research recently has focused on the role of a diet low in fermentable oligo-, di-, and mono-saccharides and polyols (FODMAPs), gluten free (GFD) and wheat free (WFD) diets for the relief of symptoms in IBS. METHODS: A round table discussion with gastroenterologists and dietitians with a specialist interest in dietary therapies in IBS was held in Sheffield, United Kingdom in May 2017. Existing literature was reviewed. PubMed and EMBASE were searched with the MeSH terms irritable bowel syndrome/diet/diet therapy/gluten/low FODMAP in different combinations to identify relevant articles. A consensus on the application of these dietary therapies into day-to-day practice was developed. RESULTS: Fourteen randomized trials in IBS evaluating the low FODMAP diet (n studies = 9), GFD (n = 4) and WFD (n = 1) were included in this review. The total number of patients recruited from randomized trials reviewed was: n=580 low FODMAP diet (female, n=430), n=203 GFD (female, n=139), n=276 WFD (female, n=215). There was no significant difference in the gender of patients recruited for both the low FODMAP and GFD randomized studies (p=0.12). The response rate in the literature to a low FODMAP diet ranged between 50-76%, and to GFD ranged between 34-71%. Percentage of IBS patients identified as wheat sensitive was reported as 30% in the literature. CONCLUSION: There are no head-to-head trials to date utilizing the low FODMAP diet, GFD and WFD for dietary treatment of IBS and still a number of concerns for diets, including nutritional inadequacy and alteration of the gut microbiota. The consensus suggests that there is evidence for the use of the low FODMAP diet, GFD and WFD as dietary therapies for IBS; the decision-making process for using each individual therapy should be directed by a detailed history by the dietitian, involving the patient in the process.
77Consensus document on exclusion diets in irritable bowel syndrome (IBS).PubMed
Francesc Casellas, Rosa Burgos, Ascensión Marcos, et al.
Nutr Hosp. 2018 Dec 3;35(6):1450-1466. doi: 10.20960/nh.2357.
This paper summarizes the contents of a consensus document on exclusion diets in irritable bowel disease that was developed by a task force from SEPD, FEAD, SENPE, FESNAD, SEÑ, SEEN, SEGHNP, SEDCA and ADENYD. The complete document is available at the FEAD and in SENPE websites. Irritable bowel syndrome is a highly prevalent functional digestive disorder where, in addition to drugs, therapy includes diet and acquisition of healthy habits as basic elements for its control. In order to facilitate dietary counseling for these patients in daily practice, the present consensus document on the role of exclusion diets was developed. To this end, consensus opinions were collected from various experts in the national scientific societies aiming at establishing recommendations applicable to the health care of patients with irritable bowel syndrome.
78Dietary and symptom assessment in adults with self-reported non-coeliac gluten sensitivity.PubMed
Gry I Skodje, Ingunn H Minelle, Kjersti L Rolfsen, et al.
Clin Nutr ESPEN. 2019 Jun;31:88-94. doi: 10.1016/j.clnesp.2019.02.012. Epub 2019 Mar 11.
BACKGROUND & AIMS: The mechanisms behind non-coeliac gluten sensitivity (NCGS) are not fully understood although clinical symptoms have shown to subside after wheat withdrawal. Self-prescription of a gluten-free diet (GFD) without medical supervision is common in NCGS subjects, resulting in dietary restrictions that can cause macro- and micronutrient deficiencies. The primary aim was to describe dietary intake, including FODMAP, in subjects with self-reported gluten sensitivity on GFD in whom coeliac disease (CD) and wheat allergy were excluded. Secondary, clinical symptoms and health-related quality of life (HR-QoL) were examined. METHODS: Baseline characteristics were obtained from 65 adults with self-reported NCGS on GFD recruited to a randomised placebo-controlled challenge trial at Oslo University Hospital. Dietary intake was obtained by a seven-day food record and symptoms recorded by questionnaires. RESULTS: Mean proportions of energy were 43 E% from fat, 40 E% from carbohydrate and 17 E% from protein. Intakes of vitamin D, folic acid, calcium, iodine and iron were lower than recommended, mean (SD) 7.3 (5.8) μg, 235 (105) μg, 695 (309) mg, 81 (52) μg and 9.6 (7.5) mg, respectively. Mean (SD) intake of FODMAP was 11.6 g (8.7). Gastrointestinal symptoms as scored by 100 mm visual analogue scale (VAS) were all below 15 mm of which wind and bloating were the most expressed. Tiredness, concentration difficulties, fatigue and muscle/joint pain were scored highest among extra-intestinal symptoms. Gastrointestinal symptoms as scored by gastrointestinal symptom rating scale - irritable bowel syndrome version (GSRS-IBS) were correlated with mild depression (r = 0.43) and inversely correlated with five sub-domains of HR-QoL (-0.29 < r < -0.26). CONCLUSION: Subjects with self-reported NCGS on GFD had high proportion of energy from fat and sub-optimal intakes of vitamin D, folic acid, calcium, iodine and iron. Despite GFD and moderate intake of FODMAP, the subjects reported various gastro- and extra-intestinal symptoms and reduced HR-QoL. The findings highlight the importance of dietary education and nutritional follow-up of subjects on GFD.
79Consensus among experts on healthy eating and diet quality index.PubMed
Simone Dos Anjos Caivano, Semíramis Martins Álvares Domene
Cien Saude Colet. 2020 Jul 8;25(7):2551-2560. doi: 10.1590/1413-81232020257.09592018.
The article aims to achieve a consensus about Healthy Eating and Diet Quality Index to enable a validation study on the Diet Quality Index. Experts were identified among authors of articles published from 2010 to 2015 that presented the key worlds healthy eating index and diet quality index. The query was carried out by combining the Delphi technique with the Likert method. To determine a consensus, at least three of the following criteria had to be met: minimum score in each statement (≥ 3,00); standard deviation (< 1,5); frequency of agreement (≥ 51%) and differences between interquartile ranges (< 1,0). Topics regarding Highly palatable foods, oilseeds, and Meat and eggs did not arrived at a consensus in the first round. Experts proposed new themes: Gluten, Meal frequency, Alcohol consumption, and Including nutrients in the diet quality index. Although quality and risk markers in diet are periodically studied, it was only possible to reach consensus on subjects such as fruits, vegetables, milk and dairy products, legumes, and oilseeds as quality markers after theoretical justification. Processed and ready-to-eat foods, highly palatable foods, excessive sweets and fats, and alcohol were readily identified as risk factors.
80Non-Celiac Gluten Sensitivity: How Its Gut Immune Activation and Potential Dietary Management Differ from Celiac Disease.PubMed
Vera Rotondi Aufiero, Alessio Fasano, Giuseppe Mazzarella
Mol Nutr Food Res. 2018 May;62(9):e1700854. doi: 10.1002/mnfr.201700854. Epub 2018 Apr 20.
Non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the ingestion of gluten-containing grains leading to intestinal and/or extraintestinal symptoms that resolve once the gluten-containing foodstuff is eliminated from the diet, and it is diagnosed when celiac disease (CD) and wheat allergy (WA) have been ruled out. The limited knowledge about the pathophysiology of NCGS and the lack of validated biomarkers are still major limitations for clinical studies, making it difficult to differentiate NCGS from other gluten-related disorders (GRD). In the absence of clear-cut diagnostic criteria, NCGS is still mainly a diagnosis of exclusion. Several studies suggest that NCGS is an immune-mediated disease that likely activates an innate immune response. Moreover, it has recently been hypothesized that in addition to gluten, other components of wheat may be responsible for the symptoms observed in individuals without CD. This review aims at discussing available evidence related to the histological and immunological features in the gut mucosa of patients with NCGS and at outlining new dietary opportunities for these patients.
81Gut microbes and adverse food reactions: Focus on gluten related disorders.PubMed
Heather J Galipeau, Elena F Verdu
Gut Microbes. 2014;5(5):594-605. doi: 10.4161/19490976.2014.969635.
Immediately following birth, the gastrointestinal tract is colonized with a complex community of bacteria, which helps shape the immune system. Under conditions of health, the immune system is able to differentiate between innocuous antigens, including food protein and commensals, and harmful antigens such as pathogens. However, patients with celiac disease (CD) develop an intolerance to gluten proteins which results in a pro-inflammatory T-cell mediated immune response with production of anti-gluten and anti-tissue transglutaminase antibodies. This adaptive immune response, in conjunction with activation of innate inflammatory cells, lead to destruction of the small intestinal mucosa. Overall 30% of the global population has genetic risk to develop CD. However, only a small proportion develop CD, suggesting that additional environmental factors must play a role in disease pathogenesis. Alterations in small intestinal microbial composition have recently been associated with active CD, indicating a possible role for the microbiota in CD. However, studies demonstrating causality are lacking. This review will highlight the recent data on the potential role of the microbiota in CD pathogenesis, the potential mechanisms, and discuss future research directions.