Review: aging-related metabolic changes in the gut-liver-heart axis and bile acids in coronary artery disease
This review proposes that aging-related metabolic changes along the gut-liver-heart axis, with bile acid metabolism as a central link, may promote coronary artery disease; most proposed interventions rest on preclinical or early-phase human data. [1]
Automatic summary · not editorially reviewed
The key findings
The review states that aging is closely associated with coronary artery disease and, in preclinical models, can promote it through immunometabolic remodeling of the gut-liver-heart axis, with bile acid metabolism proposed as a central molecular link. [1]
According to the review, age-related dysbiosis lowers bile salt hydrolase and 7α-dehydroxylase activities, contracts the secondary bile acid pool, weakens the epithelial barrier and triggers metabolic endotoxemia that maintains LPS-TLR4-NF-κB signaling. [1]
The review appraises microbiota remodeling, FXR/TGR5 agonists, senolytic therapies, metformin and integrated biomarker frameworks, noting that most are currently supported only by preclinical or early-phase human data. [1]
The source at a glance
- Study type / format
- Review abstract integrating cellular, molecular and clinical evidence
- Population / context
- Older adults and preclinical models discussed in a review of aging-associated coronary artery disease
- Summary based on
- Study abstract
- Original publication
- July 6, 2026
Aging, bile acids and coronary artery disease
The review starts from the observation that coronary artery disease is the leading cause of cardiovascular death worldwide and shows a strong age-dependence that classical risk-factor models do not fully explain. It states that aging is closely associated with coronary artery disease and, in preclinical models, can promote it through immunometabolic remodeling of the gut-liver-heart axis. Bile acid metabolism is proposed as a central molecular link in this axis. The authors integrate cellular, molecular and clinical evidence to outline how aging perturbs the axis and sustains chronic vascular inflammation.
Supporting source [1]
Proposed cellular and organ-level mechanisms
At the cellular level, senescent cells in the intestinal, hepatic and vascular compartments are described as producing the senescence-associated secretory phenotype, a process linked to cGAS-STING and NLRP3 inflammasome activation, mitochondrial dysfunction and decline of the NAD-SIRT3 axis, helping to establish systemic inflammaging. In the gut, age-related dysbiosis is said to lower bile salt hydrolase and 7α-dehydroxylase activities, shrink the secondary bile acid pool, weaken the epithelial barrier and trigger metabolic endotoxemia that maintains LPS-TLR4-NF-κB signaling. In the liver, Kupffer cell M1 polarization, attenuated farnesoid X receptor (FXR) signaling and altered exosomal cargo are said to amplify systemic inflammatory output. Reduced FXR and Takeda G-protein-coupled receptor 5 (TGR5) signaling is proposed to weaken restraint of macrophage activation, vascular smooth muscle cell phenotypic switching and cardiomyocyte metabolic protection, with endothelial dysfunction, foam cell formation, plaque instability and adverse cardiac remodeling as downstream results.
Supporting source [1]
Candidate interventions and evidence limits
The review appraises emerging immune-metabolic interventions: microbiota remodeling, FXR/TGR5 agonists, senolytic therapies, metformin, and integrated biomarker frameworks for early risk stratification. It notes that most of these are currently supported only by preclinical or early-phase human data. The authors present bile acid signaling as an interface of innate immunity, microbial ecology and metabolic homeostasis and offer an immunological framework for aging-associated coronary artery disease, identifying candidate immune-metabolic targets for prevention and therapy in older adults. These are proposed targets and a proposed framework, not validated treatments.
Supporting source [1]
How to interpret this
This is an abstract of a review integrating cellular, molecular and clinical evidence; the full text was not reviewed. The mechanisms and the gut-liver-heart axis with bile acids as a central link are proposed, and the described promotion of coronary artery disease comes from preclinical models. Most listed interventions are supported only by preclinical or early-phase human data. Associations described here are not established causes, and the proposed targets and framework are not validated treatments.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Chen W, Sun Y, Meng CF, Wu ST, Jiang XY, Meng XM, Wang QF. · europepmc.org · July 6, 2026