Bacteroides thetaiotaomicron and Bacteroides ovatus for the treatment of MAFLD: A comparative study of individual and combined effects.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing global health concern linked to gut microbiota dysbiosis. This study aims to evaluate the therapeutic effects of Bacteroidetes on MAFLD, and to explore their mechanisms. This study investigates the effects of Bacteroides thetaiotaomicron (B. thetaiotaomicron), Bacteroides ovatus (B. ovatus), and their combination on MAFLD progression in a high-fat and high-cholesterol (HFHC) diet-induced mouse model. It was indicated that both individual and combined treatments with B. thetaiotaomicron and B. ovatus effectively reduced body weight and prevented hepatic steatohepatitis and liver injury. Mechanistically, both Bacteroides species induced changes in gut microbiota diversity and composition. Treatments, whether alone or in combination, resulted in a decreased Firmicutes/Bacteroidetes (F/B) ratio, reduced abundance of Ruminococcustorques_group, Ruminococcusgauvreaui_group, and Erysipelatoclostridium, and a significant increase in the fecal abundance of Lachnospiraceae-NK4A136_group, norank_f__Oscillospiraceae, and Colidextribacter. Compared to group M, treated mice exhibited significant changes in fecal short-chain fatty acids (SCFA), decreased levels of serum lipopolysaccharides (LPS), CD163, IL-1β, TNF-α, and reduced liver macrophages. Furthermore, both M-A and M-B treatments led to the downregulation of genes involved in de novo lipogenesis (such as Srebf1, Acaca, Scd1, Fasn) and upregulation of genes related to fatty acid oxidation (such as Ppara). Combination therapy did not exhibit superior efficacy compared to individual treatments. This study provides evidence that B. thetaiotaomicron and B. ovatus can improve MAFLD by regulating the gut-liver axis, combination therapy did not exhibit superior efficacy compared to individual treatments (P>.05).