How Microbial Food Fermentation Supports a Tolerant Gut

The gastrointestinal tract harbors a complex resident microbial ecosystem, comprising over 500 species, spanning commensals, mutualist, opportunistic, and professional pathogens thriving on undigested food components originating from the diet and endogenous secretions. Despite this high concentration of food and bacterial antigens, a healthy gut has a near absent level of inflammation, a status called intestinal immune homeostasis. This immune homeostasis is built and maintained in the presence, and interestingly, with cooperation of the microbiota. The microbiota ferments undigested food components into a wide variety of metabolites, some of which interact with the intestinal immune system. In particular short-chain fatty acids, aryl hydrocarbon receptor ligands, and bile acid metabolites have been involved in the induction of intestinal immune homeostasis. The production of these metabolites is influenced by the microbial load and community structure, as well as the availability of substrates and the gut environment which are directly or indirectly modulated by food intake. In this manuscript, the factors that influence the production of these metabolites and their interaction with the immune cells that play key roles in maintaining intestinal immune homeostasis in the healthy gut are reviewed.