近年来，肠道菌群与宿主免疫系统的相互作用日益成为理解慢性炎症性疾病发病机制的关键突破口。 然而，特定共生菌代谢产物如何精准调控树突状细胞的表观遗传状态并影响其抗原呈递功能，目前仍缺乏系统性解析。 Here, we sought to identify a novel short-chain fatty acid derivative from Bifidobacterium adolescentis that modulates dendritic cell function. We discovered that this compound—termed bifilactone—specifically inhibits histone deacetylase 3 (HDAC3) in dendritic cells, leading to increased H3K27 acetylation at the Il12b promoter. This epigenetic remodeling enhances IL-12 production and promotes Th1 polarization in co-cultured CD4? T cells. In murine colitis models, oral administration of bifilactone significantly ameliorated intestinal inflammation and restored mucosal barrier integrity. Our studies demonstrate that bifilactone serves as a microbiota-derived epigenetic regulator essential for dendritic cell–mediated immune homeostasis. 该发现不仅为开发基于微生物代谢物的新型肠炎靶向干预策略提供了直接候选分子，也为后续探索菌群—表观遗传—免疫轴在其他黏膜疾病中的作用奠定了可拓展的研究范式。
