Bacteroides vulgatus alleviates non-alcoholic fatty liver disease progression by downregulating histone acetylation level via 3-HPAA Untitled Item

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disease that lacks effective interventions. Gut microbiota-based therapy may provide a new strategy for addressing this problem. In this study, we discovered Bacteroides vulgatus (B. vulgatus) as a potential probiotic of NAFLD using multi-omics analysis. Results of murine models display the supplementation of B. vulgatus alleviates the development of NAFLD. The mechanism underlying this effect is attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by B. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis to promote lipid accumulation, in liver cells. This study highlights the significant role of B. vulgatus in NAFLD development and the critical role of its metabolite 3-HPAA, which is involved in lipid homeostasis. It offers a potential solution for early intervention therapy for NAFLD.