https://orcid.org/0000-0002-3422-6927
Figures & data
Figure 1. Biotransformation and immunomodulation of microbial FAs in the intestine.
SCFAs are produced by microbial fermentation of dietary fiber. They may promote host gut immunity via GPCR-dependent mechanisms, such as signaling through epithelial GPR43/109A to activate the NLRP3 inflammasome for IL-18 secretion, or via GPCR-independent mechanisms, such as inhibiting HDACs for Treg differentiation. Branched SCFAs are derived from BCAA metabolism and have been shown to inhibit the accumulation of IgA+ plasma cells in the gut. Microbial LCFA metabolites, such as LA derivatives, are formed from microbial FA isomerization. The hydroxylated product, HYA, promotes intestinal barrier functions via epithelial GPR40 signaling, while FA isomers, namely CLAs, promote CD4+CD8αα+ IEL differentiation via HNF4G-instructed IL-18 signaling.
Table 1. The gut microbial biotransformation of lipid metabolites.
Table 2. The immunomodulatory functions of microbial lipid metabolites.
Figure 2. Biotransformation and immunomodulation of microbial BAs in the intestine.
Host-derived conjugated BAs, such as TCA, TUCDA, and TCDCA, are deconjugated by microbial BSH to produce CA, UDCA, and CDCA, while CA and CDCA are further converted to the secondary BAs DCA and LCA, respectively. DCA can inhibit the effector function of CD8+ T cells, while also undergoing oxidation and epimerization to generate isoDCA, which has gut Treg-promoting functions. LCA is converted to 3-oxoLCA and isoLCA to suppress gut Th17 differentiation, or isoalloLCA to promote gut Treg differentiation via mtROS and NR4A1. The BA pool also contributes to the development of RORγt+ Tregs via VDR. CDCA and other gut BAs can be microbially conjugated with amino acids such as tryptophan, etc. The resulting metabolites, such as Trp-CDCA, promote IFN-γ production in Th17 cells in vitro.
