Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases

• Published in: Acta pharmaceutica Sinica. B Vol. 12; no. 5; pp. 2129 - 2149
• Main Authors: Guan, Baoyi, Tong, Jinlin, Hao, Haiping, Yang, Zhixu, Chen, Keji, Xu, Hao, Wang, Anlu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2022; Elsevier
• Subjects: Bile acid; Cardiometabolic diseases; Nuclear receptors; Review; Systemic immunometabolism; Therapeutic opportunities; HNF; JNK; HFD; UDCA; NF-κB; CCs; BAs; BSH; mTOR; ASBT; SHP; CMD; BSEP; DCA; IL; FGF; HCA; PKA; IR; LCA; Nuclear receptors; PPARα; AS; FFAs; ROR; CAR; FA; Systemic immunometabolism; ERK; TMAO; FXR; Therapeutic opportunities; NAFLD; RCT; PXR; cAMP; CYP7A1; LPS; DAMPs; Cardiometabolic diseases; HDL; DCs; LDL; Bile acid; NLRP3; S1PR2; TLR; LDLR; CA; CDCA; GLP-1; VDR; ox-LDL; FMO3; NASH; OCA; CYP8B1; TGR5; TG; SCFAs; CVDs; AS, atherosclerosis; LDLR, low-density lipoprotein receptor; DCA, deoxycholic acid; JNK, c-Jun N-terminal protein kinase; ox-LDL, oxidated low-density lipoprotein; ASBT, apical sodium-dependent bile salt transporter; NAFLD, non-alcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; HCA, hyocholic acid; CA, cholic acid; FFAs, free fatty acids; PXR, pregnane X receptor; UDCA, ursodeoxycholic acid; mTOR, mammalian target of rapamycin; LCA, lithocholic acid; HFD, high fat diet; NLRP3, NLR family pyrin domain containing 3; TLR, toll-like receptor; GLP-1, glucagon-like peptide 1; CYP8B1, sterol 12α-hydroxylase; CMD, cardiometabolic disease; HNF, hepatocyte nuclear receptor; CVDs, cardiovascular diseases; IL, interleukin; CYP7A1, cholesterol 7 alpha-hydroxylase; LPS, lipopolysaccharide; VDR, vitamin D receptor; FA, fatty acids; PKA, protein kinase A; OCA, obeticholic acid; BAs, bile acids; TMAO, trimethylamine N-oxide; DCs, dendritic cells; ROR, retinoid-related orphan receptor; TG, triglyceride; cAMP, cyclic adenosine monophosphate; BSEP, bile salt export pump; FMO3, flavin-containing monooxygenase 3; S1PR2, sphingosine-1-phosphate receptor 2; SHP, small heterodimer partner; PPARα, peroxisome proliferator-activated receptor alpha; LDL, low-density lipoprotein; BSH, bile salt hydrolases; DAMPs, danger-associated molecular patterns; FXR, farnesoid X receptor; CDCA, chenodeoxycholic acid; CAR, constitutive androstane receptor; FGF, fibroblast growth factor; SCFAs, short-chain fatty acids; CCs, cholesterol crystals; RCT, reverses cholesterol transportation; ERK, extracellular signal-regulated kinase; NF-κB, nuclear factor-κB; IR, insulin resistance; HDL, high-density lipoprotein; TGR5, takeda G-protein receptor 5
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2021.12.011

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD. This review provides an updated summary and an intensive discussion about how bile acids (BAs) shape both the innate and adaptive immune system, and how BA axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of cardiometabolic disease. [Display omitted]