Li Dong-Hao, Li Zong-Wei, Sun Qi, Wang Lei, Ning Shou-Bin
Department of Gastroenterology, Air Force Medical Center of Chinese People's Liberation Army, Beijing, China.
Gut Pathog. 2024 Aug 8;16(1):42. doi: 10.1186/s13099-024-00633-9.
Recently, the oral oncobacterium Fusobacterium nucleatum (F. nucleatum), has been linked with ulcerative colitis (UC). Here, we aim to investigate whether Fecal Microbiota Transplantation (FMT) can alleviate UC by restoring gut microbiota and eliminating oral-derived F. nucleatum and virulence factor fadA.
C57BL/6J mice were randomly divided into a healthy control group (HC), Dextran Sulfate Sodium group (DSS), oral inoculation group (OR), upper FMT group (UFMT), and lower FMT group (LFMT). Disease activity index, body weight, survival rate, and histopathological scores were used to measure the severity of colitis. The function of the intestinal mucosal barrier was evaluated by performing immunohistochemical staining of the tight junction protein Occludin. Real-time PCR was used to assess the relative abundance of the nusG gene and the virulence gene fadA. Cytokine levels were detected by ELISA. Full-length sequencing of 16S rRNA was used to analyze the changes and composition of gut microbiota.
Oral incubation of F. nucleatum further exacerbated the severity of colitis and gut dysbiosis. Peptostreptococcaceae, Enterococcaceae, and Escherichia coli were significantly enriched in OR mice. However, LFMT mice showed an obvious decrease in disease activity and were more effective in restoring gut microbiota and eliminating F. nucleatum than UFMT mice. Bacteroidota, Lachnospiraceae, and Prevotellaceae were mainly enriched bacteria in LFMT mice. In addition, Genera such as Lactobacillus, Allobaculum, and Bacteroidales were found negative correlation with TNF-α, IL-1β, and IL-6. Genera like Romboutsia, Escherichia Shigella, Enterococcus, and Clostridium were found positively correlated with TNF-α, IL-1β, and IL-6.
Oral incubation of F. nucleatum further exacerbates the severity and dysbiosis in DSS-induced colitis mice. Besides, lower tract FMT can ameliorate colitis by restoring the gut microbiota diversity and eliminating F. nucleatum and virulence factor fadA.
最近，口腔致癌菌具核梭杆菌（F. nucleatum）与溃疡性结肠炎（UC）有关。在此，我们旨在研究粪便微生物群移植（FMT）是否能通过恢复肠道微生物群以及消除源自口腔的具核梭杆菌和毒力因子fadA来缓解UC。
将C57BL/6J小鼠随机分为健康对照组（HC）、葡聚糖硫酸钠组（DSS）、口服接种组（OR）、上消化道FMT组（UFMT）和下消化道FMT组（LFMT）。使用疾病活动指数、体重、存活率和组织病理学评分来衡量结肠炎的严重程度。通过对紧密连接蛋白闭合蛋白进行免疫组织化学染色来评估肠黏膜屏障的功能。使用实时PCR评估nusG基因和毒力基因fadA的相对丰度。通过酶联免疫吸附测定法检测细胞因子水平。使用16S rRNA全长测序分析肠道微生物群的变化和组成。
具核梭杆菌的口服孵育进一步加剧了结肠炎的严重程度和肠道生态失调。消化链球菌科、肠球菌科和大肠杆菌在OR小鼠中显著富集。然而，LFMT小鼠的疾病活动明显降低，并且在恢复肠道微生物群和消除具核梭杆菌方面比UFMT小鼠更有效。拟杆菌门、毛螺菌科和普雷沃氏菌科是LFMT小鼠中主要富集的细菌。此外，发现乳酸杆菌属、别氏菌属和拟杆菌目等属与肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）呈负相关。发现罗姆布茨菌属、埃希氏菌属志贺氏菌、肠球菌属和梭菌属等属与TNF-α、IL-1β和IL-6呈正相关。
具核梭杆菌的口服孵育进一步加剧了DSS诱导的结肠炎小鼠的严重程度和生态失调。此外，下消化道FMT可以通过恢复肠道微生物群多样性以及消除具核梭杆菌和毒力因子fadA来改善结肠炎。
