Gut Microbial Metabolite-Mediated Regulation of the Intestinal Barrier in the Pathogenesis of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease. The disease has a multifactorial aetiology, involving genetic, microbial as well as environmental factors. The disease pathogenesis operates at the host–microbe interface in the gut. The intestinal epithelium plays a central role in IBD disease pathogenesis. Apart from being a physical barrier, the epithelium acts as a node that integrates environmental, dietary, and microbial cues to calibrate host immune response and maintain homeostasis in the gut. IBD patients display microbial dysbiosis in the gut, combined with an increased barrier permeability that contributes to disease pathogenesis. Metabolites produced by microbes in the gut are dynamic indicators of diet, host, and microbial interplay in the gut. Microbial metabolites are actively absorbed or diffused across the intestinal lining to affect the host response in the intestine as well as at systemic sites via the engagement of cognate receptors. In this review, we summarize insights from metabolomics studies, uncovering the dynamic changes in gut metabolite profiles in IBD and their importance as potential diagnostic and prognostic biomarkers of disease. We focus on gut microbial metabolites as key regulators of the intestinal barrier and their role in the pathogenesis of IBD.

Early life administration of Bifidobacterium bifidum BD-1 alleviates long-term colitis by remodeling the gut microbiota and promoting intestinal barrier development

“…Immediately after combining these findings with our analysis of the gut microbiota after stopping treatment (on day 21), there were indeed differences in the composition of the gut microbiota after the intervention, which persisted until day 46. At day 21, ceftriaxone reduced the diversity of the microbiota and the content of SCFAs at the end of the intervention, with a decreased abundance of SCFAs-producing bacteria (such as, Alistipeshe, Clostridium_XlVa, and Bifidobacterium; Guo et al, 2017;Iyer and Corr, 2021). Early intervention with BD-1 does alter bacterial composition in terms of relative abundance, alpha diversity, and beta diversity.…”

The gut metagenomics and metabolomics signature in patients with inflammatory bowel disease

“…Microbial metabolites, including short chain fatty acids (SCFAs), tryptophan (Trp), bile acid, and vitamins are actively absorbed or diffused across the intestinal lining to affect the host response in the intestine as well as at systemic sites via the engagement of cognate receptors, influencing epithelial barrier function and intestinal homeostasis. In addition, food constituents such as micronutrients are important regulators of mucosal immunity, with direct or indirect effects on the gut microbiota, thus [ 52 ]. These findings indicate the complex molecular interaction between host’s immunity, genetics, and environmental factors in influencing gut microbiota and metabolites in IBD.…”

Unique and redundant functions of cytoplasmic actins and nonmuscle myosin II isoforms at epithelial junctions

“…Furthermore, loss of NM‐IIA in the intestinal epithelium markedly exaggerated DSS‐induced colitis, manifested by more severe epithelial erosion, infiltration of inflammatory cells, and barrier disruption 89 . Notably, increased permeability of the gut barrier has been associated with a large variety of human gastrointestinal and systemic inflammatory disorders 121–123 . Such barrier leakage is thought to contribute to the development of diseases by increasing bodily exposure to luminal bacteria, although very few tools exist to directly test such a hypothesis in vivo .…”