Flaxseed Powder Attenuates Non-Alcoholic Steatohepatitis via Modulation of Gut Microbiota and Bile Acid Metabolism through Gut–Liver Axis

Non-alcoholic steatohepatitis (NASH) is gradually becoming one of the most common and health-endangering diseases; therefore, it is very important to prevent the occurrence of NASH and prevent simple non-alcoholic fatty liver (NAFL) from further developing into NASH. We fed mice a high-fat diet (HFD, 60% fat) for 14 weeks to induce NAFL and then fed different doses of flaxseed powder (low (10%), middle (20%), and high (30%)) to the mice for 28 weeks. After the animal experiment, we analyzed fecal bile acid (BA) profiles of the HFD mice, flaxseed-fed (FLA-fed) mice, and control mice with a normal diet (10% fat) using a targeted metabolomics approach, and we analyzed the gut microbiota at the same time. We also investigated the mechanistic role of BAs in NASH and identified whether the altered BAs strongly bind to colonic FXR or TGR5. In the present study, we found that 28-week FLA treatment notably alleviated NASH development in NAFL model mice fed with an HFD, and the beneficial effects may be attributed to the regulation of and improvement in the gut flora- and microbiota-related BAs, which then activate the intestinal FXR-FGF15 and TGR5-NF-κB pathways. Our data indicate that FLA might be a promising functional food for preventing NASH through regulating microbiomes and BAs.