Pregnane X receptor

Microbiome

Receptor

Bioinformatics

Nuclear receptor

Transcription factor

Biology

Gene

Host (biology)

Innate immune system

Farnesoid X receptor

Ecology

Immunology

Metabolite

Immunity

Aryl hydrocarbon receptor

Cell biology

Biochemistry

Immune system

Summary Commensal microbes and the host immune system have been co‐evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite‐specific receptors such as P2X 7 , GPR 41, GPR 43, GPR 109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor ( PXR ), farnesoid X receptor ( FXR ), TGR 5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune‐regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article.

Immune regulation by microbiome metabolites