Lower fecal microbiota transplantation ameliorates ulcerative colitis by eliminating oral-derived Fusobacterium nucleatum and virulence factor.

IF 4.3 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Pathogens Pub Date : 2024-08-08 DOI:10.1186/s13099-024-00633-9

Dong-Hao Li, Zong-Wei Li, Qi Sun, Lei Wang, Shou-Bin Ning

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引用次数: 0

Abstract

Background: 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.

Method: 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.

Findings: 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.

Conclusions: 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.

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下粪便微生物群移植通过消除口源性核酸镰刀菌和毒力因子改善溃疡性结肠炎。

背景：最近，口服核酸镰刀菌（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、消除口源性核酸镰刀菌和毒力因子 fadA 来缓解溃疡性结肠炎：方法：将 C57BL/6J 小鼠随机分为健康对照组（HC）、右旋糖酐硫酸钠组（DSS）、口服接种组（OR）、上部 FMT 组（UFMT）和下部 FMT 组（LFMT）。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 Occludin 进行免疫组化染色来评估肠粘膜屏障的功能。实时 PCR 被用来评估 nusG 基因和毒力基因 fadA 的相对丰度。细胞因子水平通过 ELISA 检测。16S rRNA全长测序用于分析肠道微生物群的变化和组成：结果：口服核酸痢疾杆菌会进一步加剧结肠炎和肠道菌群失调的严重程度。在 OR 小鼠中，Peptostreptococcaceae、Enterococcaceae 和 Escherichia coli 显著富集。然而，与 UFMT 小鼠相比，LFMT 小鼠的疾病活动明显减少，而且在恢复肠道微生物群和消除核酸痢疾杆菌方面更为有效。LFMT小鼠体内富集的细菌主要是类杆菌科（Bacteroidota）、Lachnospiraceae和Prevotellaceae。此外，乳酸杆菌属（Lactobacillus）、乳酸菌属（Allobaculum）和类杆菌属（Bacteroidales）与 TNF-α、IL-1β 和 IL-6 呈负相关。而 Romboutsia、志贺氏杆菌、肠球菌和梭状芽孢杆菌等菌属与 TNF-α、IL-1β 和 IL-6 呈正相关：结论：口服核酸酵母菌会进一步加剧DSS诱导的小鼠结肠炎的严重程度和菌群失调。此外，下道 FMT 可通过恢复肠道微生物群的多样性、消除 F. nucleatum 和毒力因子 fadA 来改善结肠炎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY

CiteScore

7.70

自引率

2.40%

发文量

期刊介绍： Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).