Children Developing Celiac Disease Have a Distinct and Proinflammatory Gut Microbiota in the First 5 Years of Life
bioRxiv (Cold Spring Harbor Laboratory)(2020)
摘要
SUMMARY Celiac disease (CD) is an autoimmune disorder triggered by gluten consumption. To identify the role of gut microbes in CD onset, we performed a longitudinal study focusing on two important phases of gut microbiota development at ages 2.5 and 5 (n=16). We obtained samples from children who developed CD during or after the study (CD progressors) and age, sex, and HLA-matched healthy controls. CD progressors had a distinct gut microbiota composition and IgA-sequencing identified unique IgA targets in the gut. Three cytokines, one chemokine, and 19 plasma metabolites were significantly altered in CD progressors at age 5. Feeding C57BL/6J mice with taurodeoxycholic acid (TDCA), a 2-fold increased microbiota-derived metabolite in CD progressors, caused villous atrophy, increased intraepithelial lymphocytes (IELs), CD4+ T-cells, Natural Killer cells, and Qa-1 expression on T-cells while decreasing T-regulatory cells in IELs. Thus, TDCA drives inflammation in the small intestines that potentially contribute to the CD onset. Highlights CD progressors have a distinct gut microbiome composition compared to healthy controls in two important phases of gut microbiota development (age 2.5 and 5 years) CD progressors have more IgA-coated bacteria in their gut at age 5 compared to healthy controls. Further, IgA-sequencing identified unique bacterial targets in CD progressors. Three plasma proinflammatory cytokines and a chemokine were increased in CD progressors years before diagnosis, indicating an early inflammatory response. We identified 19 metabolites that are significantly altered in CD progress at age 5 and microbiota-derived TDCA increased two-fold. TDCA treatment in B6 mice increased CD4+ cells and NK cells while decreasing CD8+ T-regulatory (Treg) cells. It also increased Qa-1 expression on immune cells.
更多查看译文
关键词
proinflammatory gut microbiota,gut microbiota,celiac disease
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要