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Bile Acids and Healthy Ageing
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DOI：10.1016/j.eng.2026.01.002.png)
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Abstract
En 中文
Bile acids (BAs) comprise a class of evolutionary-conserved cholesterol metabolites that are synthesized exclusively in the liver, circulate between the liver and intestine in the so-called enterohepatic circulation, and whose structures can extensively be modulated through the actions of gut bacterial enzymes. In the past decades, it has become clear that, in addition to their classical roles in intestinal fat absorption, bile formation, and cholesterol turnover, BAs also exert hormone-like functions via activation of nuclear and membrane-bound receptors that are expressed in a variety of cell types and modulate metabolic as well as immune functions. Particularly, microbiome-derived secondary BAs have emerged as important signaling molecules with broad impact. As the gut microbiome is amendable to compositional and functional modulation, the gut–liver axis may provide opportunities for novel strategies to promote healthy ageing, such as, to prolong healthspan, in the globally ageing population. This review aims to provide an overview of available literature linking BAs to (healthy) ageing. For this purpose, it contains a general overview of BA metabolism and the importance of the gut microbiome in the modulation of BA structure and function. Additionally, it provides a comprehensive review of the current knowledge on how (microbiome-derived) BAs are associated with health and lifespan and on the mechanisms by which BAs could modulate age-related disease in specified tissues.
Keywords:
Bile acids
gut microbiome
microbiome-derived secondary bile acids
longevity
healthy ageing
gut–liver axis
senescence
inflammageing
AMPK
AMP-activated protein kinase
AR
Androgen receptor
ASBT
Apical sodium-dependent BA transporter
BAAT
Bile acid coa: amino acid N-acyltransferase
BAS-suc
bile acid acyl synthetase for succinyl
BAs
Bile acids
BMDMs
Bone marrow derived macrophages
C. elegans
Caenorhabditis elegans
CA
Cholic acid
cAMP
Cyclic AMP
CAR
Constitutive androstane receptor
CDCA
Chenodeoxycholic acid
CDKN2A
P16ink4a
CHRM2/3
Muscarinic acetylcholine receptor M2 and M3
CR
Caloric restriction
CYP27A1
Sterol 27-hydroxylase
Cyp2a12
Cytochrome P450 2A12
Cyp2c70
Cytochrome P450 2C70
CYP7A1
Cholesterol 7α-hydroxylase
D. melanogaster
Drosophila melanogaster
DA
Dafachronic acid
DCA
Deoxycholic acid
DSS
Dextran sulfate sodium
FMT
Fecal microbiota transplantation
FXR
Farnesoid x receptor
GLP-1
Glucagon-like peptide-1
GLP-1R
GLP-1 receptor
GPBAR1
G protein-coupled bile acids receptor 1
GUDCA
Glycoursodeoxycholic acid
HCC
hepatocellular carcinoma
HDCA
Hyodeoxycholic acid
HSDHs
hydroxysteroid dehydrogenases
IBD
Inflammatory bowel disease
ISCs
Intestinal stem cells
LCA
Lithocholic acid
LXR
Liver X receptor
MASLD
Metabolic dysfunction-associated steatotic liver disease
MASH
metabolic dysfunction-associated steatohepatitis
NFAT2
Nuclear factor of activated T cells 2
NKT
Natural killer T
NR4A1
Nuclear receptor subfamily 4 group A member 1
OCA
Obeticholic acid
PBC
Primary biliary cholangitis
PGC-1α
PPAR-γ coactivator 1 alpha
PKA
Protein kinase A
PMCA
Plasma membrane Ca2+ ATPase
PSC
Primary sclerosing cholangitis
PXR
Pregnane X receptor
RORγt
RAR-related orphan receptor γt
ROS
Reactive oxygen species
RXR
Retinoid-X receptor
S1PR2
Sphingosine-1-phosphate receptor 2
SASP
Senescence-associated secretory phenotype
SA-β-Gal
Senescence-associated-β-galactosidase
SCFA
Short-chain fatty acids
SIRT1
Sirtuin 1
TCA
Taurocholic acid
TGR5
Takeda G protein-coupled receptor
Th17
Inflammatory T helper 17
TMA
Trimethylamine
TMAO
Trimethylamine-N-oxide
TOR
Target of rapamycin
TUDCA
Tauroursodeoxycholic acid
TULP3
TUB-like protein 3
TβMCA
Tauro-βmca
UC
Ulcerative colitis
UDCA
Ursodeoxycholic acid
VDR
Vitamin d receptor
αMCA
Alpha-muricholic acid
βMCA
Beta-muricholic acid
3-sucCA
3-succinylated cholic acid
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