Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases.
10.1016/j.apsb.2021.12.011
- Author:
Baoyi GUAN
1
;
Jinlin TONG
1
;
Haiping HAO
2
;
Zhixu YANG
1
;
Keji CHEN
1
;
Hao XU
1
;
Anlu WANG
1
Author Information
1. Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
- Publication Type:Review
- Keywords:
AS, atherosclerosis;
ASBT, apical sodium-dependent bile salt transporter;
BAs, bile acids;
BSEP, bile salt export pump;
BSH, bile salt hydrolases;
Bile acid;
CA, cholic acid;
CAR, constitutive androstane receptor;
CCs, cholesterol crystals;
CDCA, chenodeoxycholic acid;
CMD, cardiometabolic disease;
CVDs, cardiovascular diseases;
CYP7A1, cholesterol 7 alpha-hydroxylase;
CYP8B1, sterol 12α-hydroxylase;
Cardiometabolic diseases;
DAMPs, danger-associated molecular patterns;
DCA, deoxycholic acid;
DCs, dendritic cells;
ERK, extracellular signal-regulated kinase;
FA, fatty acids;
FFAs, free fatty acids;
FGF, fibroblast growth factor;
FMO3, flavin-containing monooxygenase 3;
FXR, farnesoid X receptor;
GLP-1, glucagon-like peptide 1;
HCA, hyocholic acid;
HDL, high-density lipoprotein;
HFD, high fat diet;
HNF, hepatocyte nuclear receptor;
IL, interleukin;
IR, insulin resistance;
JNK, c-Jun N-terminal protein kinase;
LCA, lithocholic acid;
LDL, low-density lipoprotein;
LDLR, low-density lipoprotein receptor;
LPS, lipopolysaccharide;
NAFLD, non-alcoholic fatty liver disease;
NASH, nonalcoholic steatohepatitis;
NF-κB, nuclear factor-κB;
NLRP3, NLR family pyrin domain containing 3;
Nuclear receptors;
OCA, obeticholic acid;
PKA, protein kinase A;
PPARα, peroxisome proliferator-activated receptor alpha;
PXR, pregnane X receptor;
RCT, reverses cholesterol transportation;
ROR, retinoid-related orphan receptor;
S1PR2, sphingosine-1-phosphate receptor 2;
SCFAs, short-chain fatty acids;
SHP, small heterodimer partner;
Systemic immunometabolism;
TG, triglyceride;
TGR5, takeda G-protein receptor 5;
TLR, toll-like receptor;
TMAO, trimethylamine N-oxide;
Therapeutic opportunities;
UDCA, ursodeoxycholic acid;
VDR, vitamin D receptor;
cAMP, cyclic adenosine monophosphate;
mTOR, mammalian target of rapamycin;
ox-LDL, oxidated low-density lipoprotein
- From:
Acta Pharmaceutica Sinica B
2022;12(5):2129-2149
- CountryChina
- Language:English
-
Abstract:
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.
