The gut microbiota-bile acid-TGR5 axis orchestrates platelet activation and atherothrombosis.

Summary

In patients with CAD, serum deoxycholic acid was reduced and Bacteroides vulgatus was underrepresented, implicating disrupted bile acid metabolism. Using TGR5 inhibitors and knockout mice, the authors show DCA suppresses agonist-induced platelet activation and thrombosis via platelet TGR5. Oral DCA, B. vulgatus, and healthy donor stool reduced platelet hyperreactivity and thrombosis in atherosclerotic ApoE-deficient mice.

Key Findings

• Serum deoxycholic acid (DCA) is reduced and Bacteroides vulgatus is underrepresented in CAD, implicating altered bile acid metabolism.
• DCA inhibits agonist-induced platelet activation and thrombosis through platelet TGR5; pharmacological TGR5 inhibition and genetic knockout abrogate this effect.
• Oral gavage with DCA, B. vulgatus, or healthy human stool suppresses platelet hyperreactivity and thrombosis in atherosclerotic ApoE−/− mice.

Clinical Implications

Although preclinical, targeting platelet TGR5 or restoring DCA (e.g., via microbiome or bile acid modulation) could form future adjunct antithrombotic approaches beyond current antiplatelet drugs. Human translational studies are warranted to evaluate efficacy and safety.

Limitations

• Human interventional data are lacking; clinical efficacy and safety remain unknown
• Human sample sizes and subgroup characteristics are not detailed in the abstract; generalizability requires confirmation

Future Directions

Conduct early-phase clinical trials of TGR5 agonism or bile acid/microbiome modulation in thrombosis-prone CAD; define dosing, safety, and responder phenotypes; explore interactions with standard antiplatelet regimens.