期刊
ANAEROBE
卷 47, 期 -, 页码 209-217出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.anaerobe.2017.06.002
关键词
Crohn's disease; Ulcerative colitis; NF-kappa B; Gut microbiota; Metagenomic; Bacteroides vulgatus; Intraspecies
类别
资金
- University of Queensland Diamantina Institute
- Commonwealth of Australia under the International Science Linkages program [FR110013]
- CSIRO's Preventative Health Flagship Research Program
- French ANR [ANR-11-BSV6-0013]
- University of Queensland Reginald Ferguson Fellowship in Gastroenterology
- CSIRO's OCE Science Leader scheme
- Australian Government
- Agence Nationale de la Recherche (ANR) [ANR-11-BSV6-0013] Funding Source: Agence Nationale de la Recherche (ANR)
The gut microbiota is increasingly implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) although the identity of the bacteria that underpin these diseases has remained elusive. The pathobiont Bacteroides vulgatus has been associated with both diseases although relatively little is known about how its growth and functional activity might drive the host inflammatory response. We identified an ATP Binding Cassette (ABC) export system and lipoprotein in B. vulgatus ATCC 8482 and B. vulgatus PC510 that displayed significant sequence similarity to an NF-kappa B immunomodulatory regulon previously identified on a CD-derived metagenomic fosmid clone. Interestingly, the ABC export system was specifically enriched in CD subjects suggesting that it may be important for colonization and persistence in the CD gut environment. Both B. vulgatus ATCC 8482 and PC510 activated NF-kappa B in a strain and growth phase specific manner in a HT-29/kb-seap-25 enterocyte like cell line. B. vulgatus ATCC 8482 also activated NF-kappa B in a Caco-2-NF-kappa Bluc enterocyte like and an LS174T-NF-kappa Bluc goblet cell like cell lines, and induced NF-kappa B-p65 subunit nuclear translocation and IL-6, IL-8, CXCL-10 and MCP-1 gene expression. Despite this, NF-kappa B activation was not coincident with maximal expression of the ABC exporter or lipoprotein in B. vulgatus PC510 suggesting that the regulon may be necessary but not sufficient for the immunomodulatory effects. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.
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