Formononetin mitigates atherosclerosis by reducing TMAO production through modulating gut microbiota in LDLR-/- mice

Atherosclerosis is the basis of cardiovascular disease. Trimethylamine TMAO is a metabolite produced by gut microbiota, which contributes to atherogenesis. Formononetin is an isoflavonoid compound, and exhibit anti-atherogenic potential properties, but there are no reports of formononetin mitigating atherosclerosis by modulating gut microbiota to reduce TMAO production. In this study, we determined whether formononetin could attenuate atherosclerosis through modulating gut microbiota to reduce TMAO production.Some studies have shown that the oral bioavailability of formononetin is not high, so we focused formononetin attenuation of atherosclerosis on modulating gut microbiota. To verify that formononetin attenuated atherosclerosis in relation to modulating gut microbiota, we performed a faecal transplantation experiment, and the result confirmed that formononetin attenuated atherosclerosis by modulating gut microbiota.To further validate the regulatory effects of formononetin on the gut microbiota, we performed metagenomics sequencing of mouse gut microbiota. Briefly, fresh faeces were collected from mice, immediately frozen in liquid nitrogen, and transferred to a dry ice box, which was sent to Shenzhen Wekemo Information Technology Co. (Shenzhen, China), where metagenomics sequencing service and data analysis service was performed.