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

Juanjuan Wang; Ningning Zhu; Xiaomin Su; Yunhuan Gao; Rongcun Yang

doi:10.3390/cells12050793

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

Cells. 2023 Mar 2;12(5):793. doi: 10.3390/cells12050793.

Authors

Juanjuan Wang^{1

2

3}, Ningning Zhu^{1

2

3}, Xiaomin Su^{1

2

3}, Yunhuan Gao^{1

2

3}, Rongcun Yang^{1

2

3}

Affiliations

¹ Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin 300071, China.
² Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China.
³ State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.

Abstract

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.

Keywords: SCFAs; bile acid metabolites; gut microbiota; regulatory T cells; tolerogenic macrophages; tryptophan metabolites.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Epigenesis, Genetic
Fatty Acids, Volatile / metabolism
Gastrointestinal Microbiome* / physiology
Gastrointestinal Tract / metabolism
Homeostasis
Humans
Microbiota*

Substances

Fatty Acids, Volatile

Grants and funding

This research was supported by NSFC grants (grant number 81901677, 91842302, 81970457 and 91629102); the Tianjin Science and Technology Commission (grant number, 18JCZDJC35300); the Ministry of Science and Technology (grant number, 2016YFC1303604); the State Key Laboratory of Medicinal Chemical Biology and the Fundamental Research Funds for the Central University, Nankai University (63191724).