Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential

Microbial cutC-dependent production of trimethylamine (TMA) is sufficient to enhance platelet reactivity and thrombosis potential in mice.

• Gut microbes produce trimethylamine N-oxide (TMAO), which is linked to cardiovascular disease and thrombosis risks.
• The generation of TMA, a precursor to TMAO, is regulated by choline TMA-lyases encoded by cutC/D genes in human gut bacteria.
• Gnotobiotic mice studies demonstrate that microbial cutC gene expression leads to increased TMA production.
• Heightened platelet reactivity and thrombosis potential were observed in mice colonized with TMA-producing human fecal communities.
• Targeting the microbial choline TMA-lyase pathway may offer a new approach for treating atherothrombotic heart disease.

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