Institute of Biomedical Research, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China.
Department of Cardiology, Ruijin Hospital/Luwan Branch, Shanghai Jiao Tong University School of Medicine, South Chongqing Rd. No. 149, Shanghai, China.
Nat Commun. 2023 Jan 30;14(1):477. doi: 10.1038/s41467-023-36079-x.
Silymarin has been used for improving hepatic damage and lipid disorders, but its action mechanism remains to be clarified. Here, we investigate the contributions of the gut microbiota to the improvement of liver lipid metabolism by silymarin. We find i) strong and significant microbial shifts upon silymarin but not silibinin treatment; ii) over 60% variations of liver fat are explained by silymarin-induced bacterial B12 production in male rats but not in male germ-free mice; iii) fecal microbiota transplantation confirms their protective roles against liver fat accumulation; iv) upregulation of one-carbon metabolism and fatty acid degradation pathways are observed based on the liver transcriptome analyses; and v) in humans the delta changes of serum B12 associate negatively with the fluctuations of serum triglycerides. Overall, we reveal a mechanism of action underpinning the lipid-lowering effect of silymarin via the gut microbiota and its vitamin B12 producing capabilities.
水飞蓟素被用于改善肝损伤和脂质紊乱，但它的作用机制仍需阐明。在这里，我们研究了肠道微生物群对水飞蓟素改善肝脏脂质代谢的贡献。我们发现：i）水飞蓟素处理后会出现强烈而显著的微生物变化，但水飞蓟宾处理则不会；ii）在雄性大鼠中，超过 60%的肝脏脂肪变化可以用水飞蓟素诱导的细菌 B12 产生来解释，但在雄性无菌小鼠中则不能；iii）粪便微生物群移植证实了它们对肝脏脂肪积累的保护作用；iv）基于肝脏转录组分析，观察到一碳代谢和脂肪酸降解途径的上调；v）在人类中，血清 B12 的变化与血清甘油三酯的波动呈负相关。总的来说，我们揭示了水飞蓟素通过肠道微生物群及其产生维生素 B12 的能力发挥降脂作用的作用机制。
