Bridging intestinal immunity and gut microbiota by metabolites

Abstract

The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota or by the metabolism of dietary components. Here, we review the interplay between the host immune system and the microbiota, how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several major innate and adaptive immune cells involved in modulating host immune homeostasis.

Keywords: Fecal microbiota transplantation; Germ-free animals; Innate and adaptive immune cells.

Fig. 1

Tryptophan metabolic pathways in the host and microbiota. Among microbial metabolites, indole and indolic acid derivatives are the predominant Trp microbial metabolites in the gut, and the intestinal microbiota produce different metabolites based on which catalytic enzymes the bacteria produce. The kyn and serotonin pathways are the primary routes of host Trp metabolism. Trp tryptophan, TpH trytophan hydroxylase, 5-HTP 5-hydroxy tryptophan, 5-HT serotonin, IDO1 indoleamine 2,3-dioxygenase, TMO tryptophan decarboxylase, TrD tryptophan decarboxylase, ArAT aromatic amino acid aminotransferases, ILDHase indole-3-lactic acid dehydrogenase, TNA tryptophanase

Fig. 2

Biosynthesis of bile acids and microbial modification of bile acid metabolism. Cholesterol is converted into two primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), in the liver and further conjugated to glycine or taurine. The bile salts that escape active transport in the distal ileum become substrates for biotransformation reactions by intestinal bacteria. In the intestine, especially in the colon, these conjugated species are first deconjugated to CA or CDCA, and then dehydrogenated and dehydroxylated by gut bacteria into secondary bile acids such as DCA and LCA

Fig. 3

Effects of metabolites on immune cells. Metabolites derived from the microbiota or host participate in complicated host-microbiota interactions. SCFAs short chain fatty acids, AMPs antimicrobial peptides, AhR aryl hydrocarbon receptor, FXR farnesoid X receptor, PXR pregnane X receptor, HADC histone deacetylase, TJ tight junction, ILC3 group 3 innate lymphoid cell