BIFIDOBACTERIUM BREVE AND BIFIDOBACTERIUM LONGUM ATTENUATE WESTERN DIET INDUCED NON-ALCOHOLIC FATTY LIVER DISEASE

초록

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of liver disease worldwide. However, definitive medical treatments have not been established apart from lifestyle modifications. Probiotics can be a lucrative choice due to their availability, cost, and absence of severe side effects. This study aimed to elucidate the underlying mechanisms of Western diet-induced NAFLD is associated with the gut-microbiome and explore the effects of Bifidobacterium breve and B. longum from the gut-metagenomic/metabolomic profiles. Methods: Six weeks old C57BL/6J mice were fed the Western diet with/without probiotics for 8 weeks. B. breve and B. longum were administered at a concentration of 109 CFU/day. We compared liver/body weight ratios (L/B ratio), NAFLD activity score (NAS), and liver function tests. We also conducted histopathological examination of liver tissue, fecal metagenomics and metabolomics analysis, and markers for inflammation, lipogenesis, and β-oxidation in the liver. Results: Western diet induces NAFLD through dysbiosis caused by reduction in Bacteroidetes and an increase in Proteobacteria and Firmicutes phyla. Probiotics groups show significant improvements in liver enzymes (AST 113.1±34.1, P=0.005; ALT 64.4±25.83, P=0.04), L/B ratio (4.86±0.57, P<0.0001), and NAS (1.89±1.45, P=0.001) compared with the untreated group (AST 175.5±36.84; ALT 110±55.3; L/B ratio 7.07±0.75; NAS 5±1). It effectively modulated gut-microbiota mainly by enhancing the relative abundance of Bacteroidetes thereby resulting in visible changes in short-chain fatty acid and indole metabolites levels. Bifidobacterium downregulated the expression of hepatic steatosis and inflammation biomarkers (TNF-α, P=0.0006; IL-6, P=0.01; IL-1β, P=0.004) by regulating the fatty acid uptake (CD36, P<0.0001), synthesis (ACC1, P=0.003; FAS, P=0.02; DGAT, P=0.003; SREBP-1c, P=0.03; chREBP, P<0.0001), and oxidation (PPARα. P=0.01) marker. Conclusion: Bifidobacterium ameliorates NAFLD, dysbiosis, and gut metabolite through modulation of gut-microbiota resulting in reduced hepatic inflammation, steatosis, and fatty acid synthesis. Our study highlighted the association between gut-microbiota, Bifidobacterium strains, and NAFLD in the gut-liver axis.