Fusobacterium nucleatumCauses Microbial Dysbiosis and Exacerbates Visceral Hypersensitivity in a Colonization-Independent Manner
Fusobacterium nucleatumCauses Microbial Dysbiosis and Exacerbates Visceral Hypersensitivity in a Colonization-Independent Manner
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具核梭杆菌以不依赖定植的方式引起微生物失调并加剧内脏过敏
DOI：
10.3389/fmicb.2020.01281
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发表时间：
2020-06-24
影响因子：
5.2
通讯作者：
Zuo, Xiu-li
中科院分区：
文献类型：
--
作者：
Gu, Xiang;Song, Li-jin;Zuo, Xiu-li
背景：微生物失调与内脏过敏密切相关，并参与肠易激综合征（IBS）的发病机制，但起关键作用的具体菌株尚未确定。先前的生物信息学研究表明，梭杆菌是 IBS 患者和母体分离 (MS) 应激大鼠之间共有的微生物特征。在这项研究中，我们评估了具核梭杆菌 (F. nucleatum) 在 IBS 发病机制中的潜在作用。方法：获取腹泻为主的IBS（IBS-D）患者和健康对照者的粪便样本。建立 MS 大鼠模型并接受具核梭菌或生理盐水灌胃。通过结直肠扩张试验评估内脏敏感性，通过16S rRNA基因测序分析粪便微生物群。通过蛋白质印迹法评估粪便上清液中具核梭菌特异性 IgA 水平。通过质谱分析和重组大肠杆菌BL21 (DE3)的构建鉴定了与具核梭菌特异性IgA反应的抗原。结果：IBS-D 患者表现出较低的香农指数和较高的梭杆菌丰度。研究表明，具核梭菌强饲会加剧 MS 大鼠的内脏过敏，强饲具核梭杆菌和 MS 都会导致香农指数下降和粪便微生物群明显分离。此外，在灌胃具核梭菌的大鼠和IBS-D患者的粪便上清液中均检测到针对具核梭菌的特异性IgA。 FomA 蛋白是具核梭菌的主要外膜蛋白，已被证实与粪便上清液中具核梭菌的特异性 IgA 发生反应。结论：梭杆菌在 IBS-D 患者中显着增加，具核梭杆菌以不定植的方式引起微生物失调并加剧内脏过敏，从而参与 IBS 的发病机制。同时，发现具核梭菌通过 FomA 诱导特异性分泌型 IgA 增加。
Background: Microbial dysbiosis is closely associated with visceral hypersensitivity and is involved in the pathogenesis of irritable bowel syndrome (IBS), but the specific strains that play a key role have yet to be identified. Previous bioinformatic studies have demonstrated that Fusobacterium is a shared microbial feature between IBS patients and maternal separation (MS)-stressed rats. In this study, we assessed the potential role of Fusobacterium nucleatum (F. nucleatum) in the pathogenesis of IBS. Methods: Fecal samples of patients with diarrhea predominant-IBS (IBS-D) and healthy controls were obtained. An MS rat model was established to receive gavage of either F. nucleatum or normal saline. Visceral sensitivity was evaluated through colorectal distension test, and fecal microbiota was analyzed by 16S rRNA gene sequencing. F. nucleatum-specific IgA levels in fecal supernatants were assessed by western blotting. The antigen reacted with the specific IgA of F. nucleatum was identified by mass spectrometry and the construction of a recombinant Escherichia coli BL21 (DE3). Results: IBS-D patients showed a lower Shannon index and a higher abundance of Fusobacterium. The F. nucleatum-gavage was shown to exacerbate visceral hypersensitivity in MS rats, with both the F. nucleatum-gavage and MS causing a decreased Shannon index and a clear segregation of fecal microbiota. In addition, specific IgA against F. nucleatum was detected in fecal supernatants of both the F. nucleatum-gavaged rats and the IBS-D patients. The FomA protein, which is a major outer membrane protein of F. nucleatum, was confirmed to react with the specific IgA of F. nucleatum in fecal supernatants. Conclusion: Fusobacterium increased significantly in IBS-D patients, and F. nucleatum was involved in the pathogenesis of IBS by causing microbial dysbiosis and exacerbating visceral hypersensitivity in a colonization-independent manner. Meanwhile, F. nucleatum was found to induce an increase in specific secretory IgA through FomA.