Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation.

Naschla Gasaly,Marcela A Hermoso,Paul De Vos

doi:10.3389/fimmu.2021.658354

Abstract

The diverse and dynamic microbial community of the human gastrointestinal tract plays a vital role in health, with gut microbiota supporting the development and function of the gut immune barrier. Crosstalk between microbiota-gut epithelium and the gut immune system determine the individual health status, and any crosstalk disturbance may lead to chronic intestinal conditions, such as inflammatory bowel diseases (IBD) and celiac disease. Microbiota-derived metabolites are crucial mediators of host-microbial interactions. Some beneficially affect host physiology such as short-chain fatty acids (SCFAs) and secondary bile acids. Also, tryptophan catabolites determine immune responses, such as through binding to the aryl hydrocarbon receptor (AhR). AhR is abundantly present at mucosal surfaces and when activated enhances intestinal epithelial barrier function as well as regulatory immune responses. Exogenous diet-derived indoles (tryptophan) are a major source of endogenous AhR ligand precursors and together with SCFAs and secondary bile acids regulate inflammation by lowering stress in epithelium and gut immunity, and in IBD, AhR expression is downregulated together with tryptophan metabolites. Here, we present an overview of host microbiota-epithelium- gut immunity crosstalk and review how microbial-derived metabolites contribute to host immune homeostasis. Also, we discuss the therapeutic potential of bacterial catabolites for IBD and celiac disease and how essential dietary components such as dietary fibers and bacterial tryptophan catabolites may contribute to intestinal and systemic homeostasis.

Highlights

A wide range of inflammatory conditions has increased steeply in Western and developing countries, attributed to changes in the mucosal immune system, the gastrointestinal tract
inflammatory bowel disease (IBD) is a recurrent, chronic and non-specific inflammatory bowel condition that includes ulcerative colitis (UC) and Crohn’s disease (CD), disorders characterized by intermittent periods of activity or inactivity
The pathogenesis is multifactorial, and genetic predisposition occurs in 30% - 40% of the general population, only a small proportion of these individuals will develop the disease, suggesting the importance of environmental factors, with recent evidence supporting the participation of gut microbiota (GM) [3]

Summary

INTRODUCTION

A wide range of inflammatory conditions has increased steeply in Western and developing countries, attributed to changes in the mucosal immune system, the gastrointestinal tract. The pathogenesis is multifactorial, and genetic predisposition occurs in 30% - 40% of the general population, only a small proportion of these individuals will develop the disease, suggesting the importance of environmental factors, with recent evidence supporting the participation of GM [3]. This dynamic triad in the gut (mucosal immunity, GM, and diet) can be jointly explored, modulated, and enhanced for the prevention and treatment of many inflammatory diseases. We discuss the therapeutic potential of bacterial catabolites for some inflammatory conditions, such as IBD and celiac disease and how essential dietary components, such as dietary fibers and bacterial tryptophan catabolites aid intestinal and systemic homeostasis

A BRIEF DESCRIPTION OF GUT MICROBIOTA AND HOST IMMUNITY

Findings

CONCLUSIONS