Role of bile acids in liver diseases mediated by the gut microbiome

Table 1 Bile acids regulate host immunological homeostasis and inflammatory response

Title	Ref.	Target	Result
Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis	Song et al[83], 2020	BA nuclear receptors	Restoration of the intestinal BA pool can increase colonic RORγ+ Treg cell counts and ameliorate host susceptibility to inflammatory colitis
Bile acid metabolites control Th17 and Treg cell differentiation	Hang et al[48], 2019	Derivatives of LCA, 3-oxoLCA and isoalloLCA	Administration of 3-oxoLCA and isoalloLCA to mice reduced Th17 cell differentiation and increased Treg cell differentiation, respectively, in the intestinal lamina propria
Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome	Guo et al[26], 2016	Membrane receptor TGR5	Bile acids inhibited activation of the NLRP3 inflammasome via the TGR5-cAMP-PKA axis.
Gut microbiome–mediated bile acid metabolism regulates liver cancer via NKT cells	Ma et al[10], 2018	Hepatic CXCR6+ NKT cells	Microbiome uses bile acids as a messenger to accumulate NKT cells, which have an activated phenotype and inhibit liver tumor growth.
TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading	Pols et al[77], 2011	Membrane receptor TGR5	TGR5 activation in macrophages by 6a-ethyl-23(S)-methylcholic acid (6-EMCA, INT-777), a semisynthetic BA, inhibits proinflammatory cytokine production, an effect mediated by TGR5-induced cAMP signaling and subsequent NF-κB inhibition.

NKT: Natural killer T; BA: Bile acid; LCA: Lithocholic acid; TGR5: G-protein coupled bile acid receptor 1; Treg: Regulatory T; Th: T helper; PKA: Protein kinase A; RORγ: RAR-related orphan receptor gamma; NLRP3: NLR family pyrin domain containing 3.