Ellagic Acid Reduces Inulin's Adverse Effects: A Combined Approach to Enhance Therapeutic Potential in Nonalcoholic Steatohepatitis

This mouse study investigates the efficacy of ellagic acid (EA), a potent antioxidant in fruits and nuts, and inulin, a prebiotic known for gut microbiota benefits, in nonalcoholic steatohepatitis (NASH). A Western-style diet (WD) was used to induce NASH in C57BL/6J male mice for 16 weeks. Mice then received EA (100 mg/kg/day, oral gavage, 5 days/week) and/or 5% inulin (w/w in diet) for 12 weeks while continuing WD. Inulin increased energy intake and trended toward higher body weight and fasting glucose. EA reduced liver weights and restored the liver-to-body weight ratio. EA and inulin combined significantly reduced steatosis and hepatocyte ballooning, while EA alone reduced liver inflammation and improved biomarkers. In contrast, inulin alone worsened several liver parameters and increased LDL serum levels. EA, alone or combined with inulin, significantly reduced LDL. EA-treated groups showed elevated urinary 3'-methylellagic acid. Importantly, the combination of EA and inulin significantly increased urolithin A, C, and D, indicating enhanced EA metabolism and postbiotic production. While inulin alone exacerbated NASH features, EA significantly improved liver health. The combination of EA and inulin offset the adverse effects of inulin but did not further enhance the therapeutic efficacy of EA.