Huayu Qutan formula can improve platelet aggregation in acute coronary syndrome rats by regulating gut microbes to drive trimethylamine/flavin containing monooxygenase 3/trimethylamine N-oxide pathway.

Objective: To investigate the effects of gut microbes regulation of the trimethylamine (TMA)/flavin containing monooxygenase 3 (FMO3)/trimethylamine N-oxide (TMAO) pathway on platelet aggregation in acute coronary syndrome (ACS) rats and the intervention of Huayu Qutan formula.

Methods: The ACS rats with syndrome of phlegm and blood stasis rats were established. Platelet, platelet aggregation, platelet activation markers and TMA/FMO3/ TMAO pathway were detected. Metagenomics technology was employed to analyze the characteristics of the gut microbiota.

Results: Huayu Qutan formula and gut microbes could inhibit high platelet reactivity and regulate the TMA/ FMO3/TMAO pathway. The dominant bacteria in ACS rats including but not limited to the major phyla, Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, also including some low abundance phyla, Fusobacteria, Verrucomicrobia, Spirochaetes, and Deferribacteres. The dominant bacteria in the Huayu Qutan formula group were Synergistetes, Deferribacteres, Deferribacteraceae, Faecalibacterium and Mucispirillum. In the Huayu Qutan formula combined with fecal bacteria enema group, the dominant bacteria were Verrucomicrobia, Verrucomicrobiae, Akkermansia and Verrucomicrobium. These gut microbiota were correlated with pathways such as Riboflavin metabolism and Arachidonic acid metabolism.

Conclusion: Huayu Qutan formula may prevent ACS by modulating gut microbes Synergistetes, Faecalibacterium and Allobaculum, regulating the iron metabolism of Deferribacteres, and driving the TMA/FMO3/TMAO pathway to regulate gut microbiota function, and improving platelet aggregation. Akkermansia may serve as a promising probiotic, which could drive TMA/FMO3/ TMAO pathway to regulate Arachidonic acid metabolism to improve platelet aggregation. The findings of this study provide a theoretical basis for the theory of "the heart is connected with the small intestine".