Banegas Marcela, Flores-Marin David, Naskar Namrata, Correa Tulio L, Rotman Chloe, Regis Stephanie, Simpson Amelia, Chang Denis, Silvester Jocelyn, Therrien Amelie
Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA.
Am J Gastroenterol. 2025 Apr 29. doi: 10.14309/ajg.0000000000003506.
Celiac disease (CeD) is an immune-mediated enteropathy driven by gluten ingestion. Gluten challenges (GC) are commonly used to evaluate novel therapeutics and CeD mechanisms, but their associated symptom burden has not been well characterized. We aim to evaluate the proportion of subjects with gastrointestinal and extraintestinal symptoms during an experimental GC.
Pubmed, Embase, CINAHL, and Cochrane Central were searched through December 2024 for studies reporting symptoms in adult patients with CeD in remission on a gluten-free diet undergoing a GC. Studies of GC for clinical diagnosis were excluded. Eligible studies included randomized (RCT) and non-randomized trials (non-RCT) that reported symptoms. Data were pooled using random-effects meta-analysis, and heterogeneity was assessed.
We identified 48 eligible studies with a total of 1,409 participants of which 35 were included in the meta-analysis (6 RCTs, 29 non-RCTs). The most common symptoms were abdominal pain (RCT 0.56, 95% confidence interval [CI] 0.45-0.65; non-RCT 0.40, 95% CI 0.32-0.49), bloating (RCT 0.55, 95% CI 0.38 to 0.71; non-RCT 0.37, 95% CI 0.28-0.47), and nausea (0.41, 95% CI 0.24-0.59; non-RCT 0.34, 95% CI 0.24-0.46). There was significant heterogeneity across studies, with variable GC doses and durations, no systematic reporting of all symptom categories, and missing individual data for some studies. Bloating, fatigue, flatulence, and nausea were significantly more reported in studies administering ≥6 g gluten/d.
GC commonly induces gastrointestinal symptoms in patients with CeD, with abdominal pain, bloating, and nausea being most frequent. Standardized challenge protocols are needed to advance therapeutic research while minimizing symptom burden.
乳糜泻（CeD）是一种由摄入麸质引发的免疫介导性肠病。麸质激发试验（GC）常用于评估新型疗法和CeD的发病机制，但其相关的症状负担尚未得到充分描述。我们旨在评估在实验性GC期间出现胃肠道和肠外症状的受试者比例。
检索了截至2024年12月的Pubmed、Embase、CINAHL和Cochrane Central数据库，以查找关于接受GC的无麸质饮食缓解期成年CeD患者症状的研究。排除用于临床诊断的GC研究。符合条件的研究包括报告症状的随机对照试验（RCT）和非随机试验（非RCT）。使用随机效应荟萃分析汇总数据，并评估异质性。
我们确定了48项符合条件的研究，共有1409名参与者，其中35项纳入荟萃分析（6项RCT，29项非RCT）。最常见的症状是腹痛（RCT为0.56，95%置信区间[CI]0.45 - 0.65；非RCT为0.40，95%CI 0.32 - 0.49）、腹胀（RCT为0.55，95%CI 0.38至0.71；非RCT为0.37，95%CI 0.28 - 0.47）和恶心（0.41，95%CI 0.24 - 0.59；非RCT为0.34，95%CI 0.24 - 0.46）。各研究间存在显著异质性，GC剂量和持续时间各不相同，并非所有症状类别都有系统报告，部分研究缺少个体数据。在给予≥6克麸质/天的研究中，腹胀、疲劳、肠胃气胀和恶心的报告明显更多。
GC通常会在CeD患者中诱发胃肠道症状，腹痛、腹胀和恶心最为常见。需要标准化的激发试验方案来推进治疗研究，同时将症状负担降至最低。
