Targeting Desulfovibrio vulgaris flagellin-induced NAIP/NLRC4 inflammasome activation in macrophages attenuates ulcerative colitis

作者：Yaping An, Zihan Zhai, Xin Wang, Yiyun Ding, Linlin He, Lingfeng Li, Qi Mo, Chenlu Mu, Runxiang Xie, Tianyu Liu, Weilong Zhong, Bangmao Wang, Hailong Cao · 发表于：Journal of Advanced Research · 年份：2023 · DOI：10.1016/j.jare.2023.08.008 · 被引用次数：43 · 研究领域：Inflammasome and immune disorders、Inflammatory Bowel Disease、Gut microbiota and health

INTRODUCTION: The perturbations of gut microbiota could interact with excessively activated immune responses and play key roles in the etiopathogenesis of ulcerative colitis (UC). Desulfovibrio, the most predominant sulfate reducing bacteria (SRB) resided in the human gut, was observed to overgrow in patients with UC. The interactions between specific gut microbiota and drugs and their impacts on UC treatment have not been demonstrated well. OBJECTIVES: This study aimed to elucidate whether Desulfovibrio vulgaris (D. vulgaris, DSV) and its flagellin could activate nucleotide-binding oligomerization domain-like receptors (NLR) family of apoptosis inhibitory proteins (NAIP) / NLR family caspase activation and recruitment domain-containing protein 4 (NLRC4) inflammasome and promote colitis, and further evaluate the efficacy of eugeniin targeting the interaction interface of D. vulgaris flagellin (DVF) and NAIP to attenuate UC. METHODS: The abundance of DSV and the occurrence of macrophage pyroptosis in human UC tissues were investigated. Colitis in mice was established by dextran sulfate sodium (DSS) and gavaged with DSV or its purified flagellin. NAIP/NLRC4 inflammasome activation and macrophage pyroptosis were evaluated in vivo and in vitro. The effects of eugeniin on blocking the interaction of DVF and NAIP/NLRC4 and relieving colitis were also assessed. RESULTS: The abundance of DSV increased in the feces of patients with UC and was found to be associated with disease activi...