Atherosclerosis is the leading cause of cardiovascular diseases worldwide. Trimethylamine-oxide (TMAO), a metabolite of intestinal flora from dietary quaternary amines, has been shown to be closely related to the development of atherosclerosis. Previous studies have shown thatZDY01 significantly reduces the serum levels of TMAO and cecal trimethylamine (TMA) in Balb/c mice; however, its role in the inhibition of choline-induced atherosclerosis in ApoEmice remains unclear. Here, we demonstrated thatZDY01 inhibited choline-induced atherosclerosis in ApoEmice fed with 1.3% choline by reducing cecal TMA and modulating CDCA-FXR/FGF15 axis. We observed thatZDY01 decreased the cecal TMA and serum TMAO levels by utilizing cecal TMA as a nutrient, not by changing the expression of hepatic FMO3 and the composition of gut microbiota. Furthermore,ZDY01 enhanced the expression of bile acid transporters and reduced the cecal CDCA levels, thereby attenuating the FXR/FGF15 pathway, upregulating the expression of Cyp7a1, promoting reverse cholesterol transport. Taken together,ZDY01 attenuated choline-induced atherosclerosis in ApoEmice by decreasing cecal TMA and promoting reverse cholesterol transport, implying thatZDY01 treatment might have therapeutic potential in atherosclerosis. N Enterobacter aerogenes E. aerogenes E. aerogenes E. aerogenes E. aerogenes E. aerogenes -/--/--/-
