AUTHOR=Gu Xiang , Song Li-jin , Li Li-xiang , Liu Tong , Zhang Ming-ming , Li Zhen , Wang Peng , Li Ming , Zuo Xiu-li 

TITLE=Fusobacterium nucleatum Causes Microbial Dysbiosis and Exacerbates Visceral Hypersensitivity in a Colonization-Independent Manner

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01281

DOI=10.3389/fmicb.2020.01281

ISSN=1664-302X

ABSTRACT=<p><bold>Background:</bold> 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 <italic>Fusobacterium</italic> is a shared microbial feature between IBS patients and maternal separation (MS)-stressed rats. In this study, we assessed the potential role of <italic>Fusobacterium nucleatum</italic> (<italic>F. nucleatum</italic>) in the pathogenesis of IBS.</p><p><bold>Methods:</bold> 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 <italic>F. nucleatum</italic> or normal saline. Visceral sensitivity was evaluated through colorectal distension test, and fecal microbiota was analyzed by 16S rRNA gene sequencing. <italic>F. nucleatum</italic>-specific IgA levels in fecal supernatants were assessed by western blotting. The antigen reacted with the specific IgA of <italic>F. nucleatum</italic> was identified by mass spectrometry and the construction of a recombinant <italic>Escherichia coli</italic> BL21 (DE3).</p><p><bold>Results:</bold> IBS-D patients showed a lower Shannon index and a higher abundance of <italic>Fusobacterium</italic>. The <italic>F. nucleatum</italic>-gavage was shown to exacerbate visceral hypersensitivity in MS rats, with both the <italic>F. nucleatum</italic>-gavage and MS causing a decreased Shannon index and a clear segregation of fecal microbiota. In addition, specific IgA against <italic>F. nucleatum</italic> was detected in fecal supernatants of both the <italic>F. nucleatum</italic>-gavaged rats and the IBS-D patients. The FomA protein, which is a major outer membrane protein of <italic>F. nucleatum</italic>, was confirmed to react with the specific IgA of <italic>F. nucleatum</italic> in fecal supernatants.</p><p><bold>Conclusion:</bold><italic>Fusobacterium</italic> increased significantly in IBS-D patients, and <italic>F. nucleatum</italic> was involved in the pathogenesis of IBS by causing microbial dysbiosis and exacerbating visceral hypersensitivity in a colonization-independent manner. Meanwhile, <italic>F. nucleatum</italic> was found to induce an increase in specific secretory IgA through FomA.</p>