<em><strong>Bacteroides vulgatus</strong></em><strong> alleviates non-alcoholic fatty liver disease progression by downregulating histone acetylation level via 3-HPAA</strong> 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 <em>Bacteroides vulgatus (B. vulgatus) </em>as a potential probiotic of NAFLD using multi-omics analysis. Results of murine models display the supplementation of <em>B. vulgatus</em> alleviates the development of NAFLD. The mechanism underlying this effect is attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by <em>B. vulgatus</em>, which reduces the acetylation levels of H3K27 and downregulates the transcription of <em>Squalene Epoxidase (SQLE)</em>, a rate-limiting enzyme in steroid biosynthesis to promote lipid accumulation, in liver cells. This study highlights the significant role of <em>B. vulgatus</em> 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.非酒精性脂肪性肝病（Non-alcoholic fatty liver disease, NAFLD）是一种高发的代谢性疾病，目前尚缺乏有效的干预手段。基于肠道菌群的治疗策略或许可为解决该问题提供新的思路。本研究通过多组学分析，筛选出普通拟杆菌（Bacteroides vulgatus, B. vulgatus）作为非酒精性脂肪性肝病的潜在益生菌。小鼠模型实验结果显示，补充普通拟杆菌可缓解非酒精性脂肪性肝病的病程进展。该作用的机制归因于普通拟杆菌产生的代谢物3-羟基苯乙酸（3-Hydroxyphenylacetic acid, 3-HPAA），其可降低肝细胞内H3K27的乙酰化水平，并下调类固醇生物合成中促进脂质积累的限速酶鲨烯环氧酶（Squalene Epoxidase, SQLE）的转录，进而抑制脂质积累。本研究阐明了普通拟杆菌在非酒精性脂肪性肝病发生发展中的重要作用，及其代谢物3-HPAA在脂质稳态调控中的关键功能，为非酒精性脂肪性肝病的早期干预治疗提供了潜在方案。