ArticleEndocrine, metabolic & immune disorders drug targets2026
Dissecting the Gut Microbiota-metabolite-coronary Atherosclerosis Axis: Evidence from Two-sample Mendelian Randomization.
Article in Endocrine, metabolic & immune disorders drug targets, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionCoronary Atherosclerosis (CAS) is a complex disease influenced by host genes, the gut microbiota, and circulating metabolites. Causal relationships and mediating effects among these factors have not yet been clarified.
methodsA two-sample Mendelian Randomization (MR) study was conducted using genomewide association study data from FinnGen, OpenGWAS, and Canadian Longitudinal Study on Aging. A total of 473 genetic instruments for gut microbial traits and 1,400 for plasma metabolites were selected. We applied bidirectional Mendelian randomization, sensitivity tests, and two-step mediation analysis to assess causal effects and identify metabolic mediators.
results18 gut microbiota taxa and 36 metabolites that are associated with coronary atherosclerosis. Protective taxa included DISCUSSION: These findings provide genetic evidence for the involvement of the gut microbiota in the development of coronary atherosclerosis, which may occur through metabolic pathways. Beneficial microbial taxa may be preferentially sustained by amino acid metabolism and anti-inflammatory mediators, whereas pathogenic taxa tend to proliferate under conditions characterized by lipid and sterol metabolic dysregulation.
conclusionThis study emphasizes the potential central axis of gut microbiota-plasma metabolites- CAS and identifies microbial and plasma metabolite candidates that may serve as targets for early prevention and intervention of CAS. These findings provide new insights into the molecular mechanisms underlying the interactions between gut microbiota and plasma metabolites in the development and progression of CAS, and offer a reference for future exploration of precision medicine strategies targeting CAS.
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