Ligustrum Robustum Alleviates Atherosclerosis by Decreasing Serum TMAO, Modulating Gut Microbiota and Decreasing Bile acid and Cholesterol Absorption in Mice.

Scope Atherosclerosis (AS) is closely related to gut microbiota. Our previous studies demonstrated that Ligustrum robustum (LR), a flavonoid-rich tea like plant, could mitigate several AS-related risk factors and modulate gut microbiota in animal models and human subjects. But its anti-AS effect and mechanisms remain unclear. Therefore, in this study, we investigated impacts of LR on AS development and explored the potential underlying mechanisms in C57BL/6J and Apoe-/- mice. Methods and results Female C57BL/6J and Apoe-/ - mice were fed a chow diet or high-choline diet, supplemented with vehicle (water) or LR water extract (700 mg/kg) by gavage for 17 weeks. We found that LR attenuated diet-induced AS by reducing serum trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) levels likely by modulating gut microbiota. Moreover, LR increased the abundance of the genus Bifidobacterium, which generated bile salt hydrolase, and thus presumably enhanced bile acid (BA) deconjugation and increased fecal BA excretion. Meanwhile, LR increased fecal cholesterol excretion, decreased the levels of serum and hepatic cholesterol, but did not affect short-chain fatty acids (SCFAs) in feces. Conclusion LR attenuated AS development presumably by decreasing serum TMAO levels and increasing fecal BA excretion likely via gut microbial modulation. These effects were accompanied by increases in fecal cholesterol excretion, decreases in serum and hepatic cholesterol. This article is protected by copyright. All rights reserved.