文献类型：期刊文献

英文题名：Fusobacterium varium Exacerbates Neutrophil-driven Intestinal Inflammation Associated with Succinate-SUCNR1-NF-κB Signaling

作者：Wang, Qian[1,2];Xiao, Han[1,2];Liu, Wenxiu[1,2];Dang, Xiangji[2,4];Bai, Yanrui[1,2];Xiao, Ruihong[1,2];Tong, Liyu[1,2];Wang, Yan[1,2];Li, Mi[5,6,7];Wang, Shuhan[1,2];Pu, Sugui[2,8];Pei, Duoji[9];Zhang, Dekui[2,8];Wang, Xiang[2,8];Hu, Guang[10];Guo, Jingjing[11];Jin, Xiaojie[5,6,7];Qin, Long[1,2];Zhang, Chunjiang;Li, Yana[12];Zhang, Tiansheng[3];Yang, Jing[1,2];Wang, Qi[1,2,13];Sun, Hui[1,2,3]

第一作者：Wang, Qian

通信作者：Sun, H[1];Sun, H[2];Sun, H[3]

机构：[1]Lanzhou Univ, Hosp 2, Cuiying Biomed Res Ctr, Lanzhou 730030, Gansu, Peoples R China;[2]Lanzhou Univ, Clin Med Sch, Lanzhou 730030, Gansu, Peoples R China;[3]Lanzhou Huazhitiancheng Biotechnol Co Ltd, Lanzhou 730030, Gansu, Peoples R China;[4]Lanzhou Univ, Hosp 2, Dept Pharm, Lanzhou 730030, Gansu, Peoples R China;[5]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730030, Gansu, Peoples R China;[6]Gansu Univ Chinese Med, Key Lab Dunhuang Med, Minist Educ, Lanzhou 730030, Gansu, Peoples R China;[7]Gansu Pharmaceut Ind Innovat Res Inst, Lanzhou 730030, Gansu, Peoples R China;[8]Lanzhou Univ, Hosp 2, Lanzhou 730030, Gansu, Peoples R China;[9]Monash Univ, Clayton, Vic 3800, Australia;[10]Soochow Univ, Sch Life Sci, Dept Bioinformat & Computat Biol, MOE Key Lab Geriatr Dis & Immunol,Suzhou Med Coll, Suzhou 215123, Jiangsu, Peoples R China;[11]Macao Polytech Univ, Fac Appl Sci, Ctr Artificial Intelligence Driven Drug Discovery, Macau 999078, Peoples R China;[12]Binzhou Med Univ, Sch Basic Med, Dept Pathophysiol, Yantai 264100, Shandong, Peoples R China;[13]Gansu Prov Key Lab Environm Oncol, Lanzhou 730030, Gansu, Peoples R China

第一机构：Lanzhou Univ, Hosp 2, Cuiying Biomed Res Ctr, Lanzhou 730030, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 2, Cuiying Biomed Res Ctr, Lanzhou 730030, Gansu, Peoples R China;[2]corresponding author), Lanzhou Univ, Clin Med Sch, Lanzhou 730030, Gansu, Peoples R China;[3]corresponding author), Lanzhou Huazhitiancheng Biotechnol Co Ltd, Lanzhou 730030, Gansu, Peoples R China.

年份：2026

卷号：49

期号：1

外文期刊名：INFLAMMATION

收录：;Scopus(收录号：2-s2.0-105048798387);WOS:【SCI-EXPANDED(收录号:WOS:001862656500001)】；

基金：This work was funded by National Natural Science Foundation of China (82572004), the Fundamental Research Funds for the Central Universities (lzujbky-2023-eyt04), Key Research and Development Program of Gansu Province (25YFFA067), Gansu Provincial Major Science and Technology Special Project Plan (24ZDNA003), Gansu Province key talent project (2023RCXM65), Lanzhou Talent Innovation and Entrepreneurship Project (2021-RC-115), Talent Introduction Plan of the Second Hospital of Lanzhou University (yjrckyqdj-2020-01, yjrckyqdj-2022-01), and the Longyuan Youth Talent Program of Gansu Province (to J.Y.).

语种：英文

外文关键词：Fusobacterium varium; Ulcerative colitis; Neutrophils; NF-kappa B; Succinate

摘要：Disruption of gut microbial homeostasis is a hallmark of ulcerative colitis (UC), yet the specific pathobionts and effector molecules driving mucosal inflammation remain unclear. In this study, metagenomic sequencing of fecal samples from 37 patients with UC and 30 healthy controls was performed to identify differentially enriched bacterial species. Fusobacterium varium (F. varium) was found to be significantly enriched in patients with UC and was therefore selected for further functional investigation. Germ-free mice colonized with F. varium developed more severe dextran sulfate sodium (DSS)-induced colitis, accompanied by enhanced mucosal inflammation. In addition, F. varium culture supernatants increased NF-kappa B reporter activity and inflammatory signaling at the protein level. Bioactivity-guided fractionation combined with mass spectrometry identified succinate as a major candidate bacterial-derived bioactive metabolite. Succinate exacerbated colonic inflammation in vivo and promoted neutrophil recruitment, whereas inhibition of CXCR2 signaling reduced neutrophil infiltration and alleviated disease severity. In vitro experiments further demonstrated that succinate activated NF-kappa B signaling in HL-60-derived neutrophils through succinate receptor 1 (SUCNR1) and induced the production of inflammatory mediators, including CXCL8. Collectively, these findings support a role for F. varium in exacerbating intestinal inflammation under colitic conditions, at least in part through succinate-associated neutrophil recruitment.