한빛사 논문
Chil-sung Kang1, Mingi Ban1, Eun-Jeong Choi1, Hyung-Geun Moon1, Jun-Sung Jeon1, Dae-Kyum Kim1, Soo-Kyung Park2, Seong Gyu Jeon1, Tae-Young Roh1, Seung-Jae Myung2, Yong Song Gho1*#, Jae Gyu Kim3*#, Yoon-Keun Kim1*#
1Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea,
2Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,
3Department of Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea
#These authors contributed equally to this work.
*Corresponding author
Abstract
Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.
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