The gut bacterium and pathobiont Bacteroides vulgatus activates NF-κB in a human gut epithelial cell line in a strain and growth phase dependent manner

- The pathobiont Bacteroides vulgatus has been implicated in the etiology of both Crohn's disease and ulcerative colitis.
- However, 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 ATCC8482 and B. vulgatus PC510.
- The ABC system is similar to an NF-κB immunomodulatory regulon previously identified on a CD-derived metagenomic fosmid.
- The ABC system was enriched in CD subjects suggesting it is important to colonize and persist in the CD gut environment.
- B. vulgatus activated NF-κB in a gut epithelial enterocyte and goblet cell line in a strain and growth phase specific manner.
- B. vulgatus ATCC8482 also induced NF-κB-p65 subunit nuclear translocation and expression of IL-6, IL-8, CXCL-10 and MCP-1.
- NF-κB activation was not coincident with maximal expression of the ABC exporter or lipoprotein in B. vulgatus PC510.

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-κB 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-κB 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-κB in a Caco-2-NF-κBluc enterocyte like and an LS174T-NF-κBluc goblet cell like cell lines, and induced NF-κB-p65 subunit nuclear translocation and IL-6, IL-8, CXCL-10 and MCP-1 gene expression. Despite this, NF-κB 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.