Amelioration of Hepatic Steatosis in Mice through Bacteroides uniformis CBA7346-Mediated Regulation of High-Fat Diet-Induced Insulin Resistance and Lipogenesis

Abstract

Dietary habits and gut microbiota play an essential role in non-alcoholic fatty liver disease (NAFLD) and related factors such as insulin resistance and de novo lipogenesis. In this study, we investigated the protective effects of Bacteroides uniformis CBA7346, isolated from the gut of healthy Koreans, on mice with high-fat diet (HFD)-induced NAFLD. Administration of B. uniformis CBA7346 reduced body and liver weight gain, serum alanine aminotransferase and aspartate aminotransferase levels, liver steatosis, and liver triglyceride levels in mice on an HFD; the strain also decreased homeostatic model assessment for insulin resistance values, as well as serum cholesterol, triglyceride, lipopolysaccharide, leptin, and adiponectin levels in mice on an HFD. Moreover, B. uniformis CBA7346 controlled fatty liver disease by attenuating steatosis and inflammation and regulating de novo lipogenesis-related proteins in mice on an HFD. Taken together, these findings suggest that B. uniformis CBA7346 ameliorates HFD-induced NAFLD by reducing insulin resistance and regulating de novo lipogenesis in obese mice.

Modulation of the gut microbiome and Firmicutes phylum reduction by a nutraceutical blend in the obesity mouse model and overweight humans: A double‐blind clinical trial

“…This species has been associated with normal weight in adolescents (Del Chierico et al., 2018 ) and is considered a predictor of weight loss (Bischoff et al., 2022 ). Furthermore, the supplement increased the abundance of Bacteroides uniformis , contributing to elevated gut folate levels, regulating liver lipid metabolism (Roelofs et al., 2016 ), and constituting a part of the gut microbiota (Lee et al., 2021 ). Consistently, in our obese mice model, the supplement similarly elevated the abundance of the Bacteroidaceae family and the Bacteroides genus (Nehmi‐Filho, de Freitas, et al., 2023 ).…”

Protective Effect of Vegan Microbiota on Liver Steatosis Is Conveyed by Dietary Fiber: Implications for Fecal Microbiota Transfer Therapy

“…The depletion of B. uniformis was found in NAFLD [ 50 , 51 ] in observational studies. Treatment with B. uniformis , particularly when combined with fiber, ameliorated diet-induced hepatic steatosis and inflammation, restored the compromised intestinal immune defense, and improved whole-body glucose disposal [ 52 , 53 ]. Qiao et al proposed the mechanism of the beneficial effect of B. uniformis.…”

Diet and Gut Microbiota Interaction-Derived Metabolites and Intrahepatic Immune Response in NAFLD Development and Treatment

“…Pediatric NAFLD patients treated with a probiotic capsule, including Lactobacillus acidophilus (ATCC B3208), Bifidobacterium lactis (DSMZ 32269), Bifidobacterium bifidum (ATCC SD6576), Lactobacillus rhamnosus (DSMZ 21690) for 12 weeks showed reduced liver injury and a higher percentage of normal liver sonography in compared to placebo treatment [ 93 ]. Administration of Bacteroides uniformis (CBA7346), a strain isolated from the healthy human gut, can ameliorate liver injury, inflammation, and lipid accumulation in NAFLD mice induced by feeding an HFD via improving insulin resistance and regulating de novo lipogenesis-related proteins, such as fatty acid synthase (FAS) and peroxisome proliferator-activated receptor-gamma (PPARγ) [ 94 ].…”