Silymarin, a mixture of flavonolignans (with silibinin being the major component1) and some other polyphenolic compounds such as taxifolin2, has long been known with diverse hepatoprotective properties such as antioxidant and lipid-lowering effects3,4and could improve non-alcoholic fatty liver diseases (NAFLD)5,6. The corresponding clinical studies of silymarin have been comprehensively reviewed recently7. Although moderate improvements on liver functions and fibrosis have been observed, controversies exist among reported clinical trials potentially due to differences in sample size and treatment duration7. In addition, the dose effects and poor absorption observed for this drug might also play a role and it has been observed that the concentrations required for many of the known pharmacological effects of silymarin are hardly achievable in both animals (~0.73%)8and humans (~1–2%)9. Thus, the action mechanisms of silymarin and its hepatoprotective benefits warrant further elucidation. Of interest, after oral administration, silymarin similar to metformin10,11, has been observed with a high concentration in the gastrointestinal tract. Whether the lipid-lowing effect of silymarin works through gut microbiota resembling the glucose-lowering effect of metformin12still needs further investigation.
To address this, we studied the improvement of liver lipid metabolism after supplementation of silymarin or silibinin for 12 weeks in obese rats and profiled the gut microbiota on collected fecal samples using 16s rRNA sequencing. A subset of fecal DNA samples was then subjected to whole genomics shotgun (WGS) and targeted metabolomics for characterization of the microbial functional changes upon silymarin treatment. We also performed the germ-free mice and fecal microbiota transplantation (FMT) experiments to explore the causality and liver RNA sequencing to identify the potential target genes in the liver by the gut microbes and associated metabolites.
