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Review
. 2023 May 15:14:1127743.
doi: 10.3389/fimmu.2023.1127743. eCollection 2023.

Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity

Xiaomin Su  1   2   3 , Yunhuan Gao  1   2   3 , Rongcun Yang  1   2   3
Affiliations
Review

Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity

Xiaomin Su et al. Front Immunol. .

Abstract

Bile acids (BAs) as cholesterol-derived molecules play an essential role in some physiological processes such as nutrient absorption, glucose homeostasis and regulation of energy expenditure. They are synthesized in the liver as primary BAs such as cholic acid (CA), chenodeoxycholic acid (CDCA) and conjugated forms. A variety of secondary BAs such as deoxycholic acid (DCA) and lithocholic acid (LCA) and their derivatives is synthesized in the intestine through the involvement of various microorganisms. In addition to essential physiological functions, BAs and their metabolites are also involved in the differentiation and functions of innate and adaptive immune cells such as macrophages (Macs), dendritic cells (DCs), myeloid derived suppressive cells (MDSCs), regulatory T cells (Treg), Breg cells, T helper (Th)17 cells, CD4 Th1 and Th2 cells, CD8 cells, B cells and NKT cells. Dysregulation of the BAs and their metabolites also affects development of some diseases such as inflammatory bowel diseases. We here summarize recent advances in how BAs and their metabolites maintain gut and systemic homeostasis, including the metabolism of the BAs and their derivatives, the role of BAs and their metabolites in the differentiation and function of immune cells, and the effects of BAs and their metabolites on immune-associated disorders.

Keywords: bile acids; deoxycholic acid; gut microbiota; lithocholic acid; regulatory B cells; regulatory T cells; tolerogenic macrophages.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Gut microbiota is not only involved in the generation of conjugated BAs, but also plays a critical role in the transformation of BAs from conjugated BAs to deconjugated BAs and the generation of secondary BAs DCA and LCA and their derivatives.
Figure 2
Figure 2
Regulations of BAs and their derivatives on the differentiation and function of immune cells for gut and systemic homeostasis. BAs and their derivatives not only promote the generation and function of anti-inflammatory cells, but also inhibit inflammatory cells through different receptors in the immune cells.
Figure 3
Figure 3
Regulation of BAs and their derivatives on the differentiation of Tregs. BA derivative isoDCA increases Foxp3 induction by diminishing DC immunostimulatory properties. IsoalloLCA promotes the differentiation of Treg cells through the production of mitochondrial reactive oxygen species, which lead to increased expression of Foxp3. Nuclear hormone receptor NR4A1 is also required for the effect of isoalloLCA on Treg cells. In addition, a distinct Treg population expressing the transcriptional factor RORγ is also induced in the colonic lamina propria by BAs and their metabolites.
Figure 4
Figure 4
BAs and their metabolites are related to the occurrence and development of immune-associated disorders such as gut diseases (inflammatory bowel disease, coeliac disease and irritable bowel syndrome), metabolic diseases (obesity, type 2 disbetes, cardiovascular disease and nonalcoholic fatty liver disease), tumor (such as colorectal cancer and liver cancer), neurodegenerative disease (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Multiple sclerosis), allergic diseases, autoimmune diseases and infections (such as bacterium infection). Red dotted lines indicate that BAs and their metabolites in virus infection can also promote innate immunes.
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Grants and funding

This research was supported by NSFC grants 91842302, 81970488, 91029736, 9162910, 91442111 and 31570114.