Harringer Emma Olivia Schultz, Durack Juliana, Piceno Yvette, Andersen Vibeke, Lynch Susan V
Department of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, CA 94143, USA.
Molecular Diagnostics and Clinical Research Unit, IRS-Centre Soenderjylland, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark.
Microorganisms. 2022 Dec 21;11(1):12. doi: 10.3390/microorganisms11010012.
Several studies have reported improved disease symptomatology in ulcerative colitis (UC) patients consuming a gluten free diet. This observation coupled with diversity depletion in the gut microbiota of UC patients led us to hypothesize that UC-associated enteric microbes differentially metabolize dietary gluten to produce immunogenic products that promote inflammation. Gluten concentration in stool was determined using gluten-specific ELISA, and gluten intake was assessed by food frequency questionnaire (FFQ) in UC (n = 12) and healthy controls (HC; n = 13). Gluten-metabolizing bacteria were isolated on minimal media supplemented with 1% gluten from UC and HC and identified by 16S rRNA profiling. Cell-free culture media from gluten metabolizing gut bacterial isolates was assessed for immunogenicity in vitro using HT29 colonocytes. Compared to HC, UC patients did not consume gluten differently (Mann−Whitney; p > 0.10) and exhibited equivalent levels of gluten in their feces (Mann−Whitney; p = 0.163). The profile of gluten-degrading bacteria isolated from UC stool was distinct (Chi-square; p ≤ 0.0001). Compared with Enterococcus isolates, products of gluten degradation by Bacillus strains induced higher IL8 and lower occludin (Mann−Whitney; p = 0.002 and p = 0.059, respectively) gene expression in colonocytes irrespective of whether they originated from UC or healthy gut. Members of HC and UC microbiota exhibit gluten-degrading ability, metabolites of which influence genes involved in inflammation and barrier function in enteric colonocyte cultures. Preliminary findings of this study warrant further investigations into the mechanisms by which gut microbiota contribute to UC pathogenesis through gluten degradation.
多项研究报告称，食用无麸质饮食的溃疡性结肠炎（UC）患者的疾病症状有所改善。这一观察结果加上UC患者肠道微生物群的多样性减少，促使我们提出假设，即与UC相关的肠道微生物以不同方式代谢膳食麸质，从而产生促进炎症的免疫原性产物。使用麸质特异性酶联免疫吸附测定法（ELISA）测定粪便中的麸质浓度，并通过食物频率问卷（FFQ）评估UC患者（n = 12）和健康对照者（HC；n = 13）的麸质摄入量。从UC和HC患者中分离出在添加1%麸质的基本培养基上生长的麸质代谢细菌，并通过16S rRNA分析进行鉴定。使用HT29结肠细胞在体外评估麸质代谢肠道细菌分离株的无细胞培养基的免疫原性。与HC相比，UC患者的麸质摄入量没有差异（曼-惠特尼检验；p > 0.10），且粪便中的麸质水平相当（曼-惠特尼检验；p = 0.163）。从UC粪便中分离出的麸质降解细菌的图谱不同（卡方检验；p ≤ 0.0001）。与肠球菌分离株相比，无论其源自UC还是健康肠道，芽孢杆菌菌株降解麸质的产物在结肠细胞中诱导更高的IL8基因表达和更低的闭合蛋白基因表达（曼-惠特尼检验；分别为p = 0.002和p = 0.059）。HC和UC微生物群的成员均表现出麸质降解能力，其代谢产物会影响肠道结肠细胞培养物中参与炎症和屏障功能的基因。本研究的初步结果值得进一步研究肠道微生物群通过麸质降解促进UC发病机制的研究。
