Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis

The gut microbiota, including bacteria, archaea, fungi, viruses and phages, inhabits the gastrointestinal tract. This commensal microbiota can contribute to the regulation of host immune response and homeostasis. Alterations of the gut microbiota have been found in many immune-related diseases. The metabolites generated by specific microorganisms in the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan (Trp) and bile acid (BA) metabolites, not only affect genetic and epigenetic regulation but also impact metabolism in the immune cells, including immunosuppressive and inflammatory cells. The immunosuppressive cells (such as tolerogenic macrophages (tMacs), tolerogenic dendritic cells (tDCs), myeloid-derived suppressive cells (MDSCs), regulatory T cells (Tregs), regulatory B cells (Breg) and innate lymphocytes (ILCs)) and inflammatory cells (such as inflammatory Macs (iMacs), DCs, CD4 T helper (Th)1, CD4Th2, Th17, natural killer (NK) T cells, NK cells and neutrophils) can express different receptors for SCFAs, Trp and BA metabolites from different microorganisms. Activation of these receptors not only promotes the differentiation and function of immunosuppressive cells but also inhibits inflammatory cells, causing the reprogramming of the local and systemic immune system to maintain the homeostasis of the individuals. We here will summarize the recent advances in understanding the metabolism of SCFAs, Trp and BA in the gut microbiota and the effects of SCFAs, Trp and BA metabolites on gut and systemic immune homeostasis, especially on the differentiation and functions of the immune cells.

Automated summary

The gut microbiota, which consists of bacteria, archaea, fungi, viruses, and phages, plays a role in regulating the host immune response and maintaining homeostasis. Changes in the gut microbiota have been linked to immune-related diseases. Metabolites produced by specific microorganisms in the gut, such as SCFAs, Trp, and BA, affect genetic and epigenetic regulation as well as metabolism in immune cells. These metabolites activate receptors on immunosuppressive and inflammatory cells, promoting the differentiation and function of the former while inhibiting the latter, thereby maintaining immune homeostasis. This review summarizes recent research on the metabolism of SCFAs, Trp, and BA in the gut microbiota and their effects on gut and systemic immune homeostasis, particularly on immune cell differentiation and functions.