A Freshwater Fish-Based Diet Alleviates Liver Steatosis by Modulating Gut Microbiota and Metabolites: A Clinical Randomized Controlled Trial in Chinese Participants With Nonalcoholic Fatty Liver Disease

We aimed to assess the effects of 2 isoenergetic intervention diets (a freshwater fish-based diet [F group] or freshwater fish-based and red meat-based diets alternately [F/M group]) on liver steatosis and their relationship with intestinal flora in patients with nonalcoholic fatty liver disease (NAFLD).In this open-label, 84-day randomized controlled trial, 34 NAFLD patients with hepatic steatosis ≥10% were randomly assigned to the F group or F/M group in a 1:1 ratio using a computer-generated random number allocation by a researcher not involved in the study. Liver fat content and gut microbiota and its metabolites were measured.At the end of intervention, the absolute reduction of hepatic steatosis was significantly greater in the F group than in the F/M group (-4.89% vs -1.83%, P = 0.032). Of the 16 secondary clinical outcomes, the improvement in 7 in the F group was greater compared with the F/M group, including alanine aminotransferase and gamma-glutamyl transferase. Furthermore, dietary freshwater fish and red meat consumption alternately did not exacerbate NAFLD. Moreover, changes in the enrichment of Faecalibacterium, short-chain fatty acids, and unconjugated bile acids and the depletion of Prevotella 9 and conjugated bile acids in the F group were significantly greater compared with the F/M group.Higher intake of freshwater fish may be beneficial to NAFLD by regulating gut microbiota and its metabolites, whereas intake of a similar total of animal protein and fat from the alternating freshwater fish and red meat may not be harmful for NAFLD in the dietary management of patients with NAFLD.