| Autor: |
Singh V, West G, Fiocchi C, Good CE, Katz J, Jacobs MR, Dichosa AEK, Flask C, Wesolowski M, McColl C, Grubb B, Ahmed S, Bank NC, Thamma K, Bederman I, Erokwu B, Yang X, Sundrud MS, Menghini P, Basson AR, Ezeji J, Viswanath SE, Veloo A, Sykes DB, Cominelli F, Rodriguez-Palacios A |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 10. Date of Electronic Publication: 2024 Jan 10. |
| DOI: |
10.1101/2024.01.09.574896 |
| Abstrakt: |
Crohn's disease (CD) has been traditionally viewed as a chronic inflammatory disease that cause gut wall thickening and complications, including fistulas, by mechanisms not understood. By focusing on Parabacteroides distasonis (presumed modern succinate-producing commensal probiotic), recovered from intestinal microfistulous tracts (cavernous fistulous micropathologies CavFT proposed as intermediate between 'mucosal fissures' and 'fistulas') in two patients that required surgery to remove CD-damaged ilea, we demonstrate that such isolates exert pathogenic/pathobiont roles in mouse models of CD. Our isolates are clonally-related; potentially emerging as transmissible in the community and mice; proinflammatory and adapted to the ileum of germ-free mice prone to CD-like ileitis (SAMP1/YitFc) but not healthy mice (C57BL/6J), and cytotoxic/ATP-depleting to HoxB8-immortalized bone marrow derived myeloid cells from SAMP1/YitFc mice when concurrently exposed to succinate and extracts from CavFT-derived E. coli , but not to cells from healthy mice. With unique genomic features supporting recent genetic exchange with Bacteroides fragilis -BGF539, evidence of international presence in primarily human metagenome databases, these CavFT Pdis isolates could represent to a new opportunistic Parabacteroides species, or subspecies (' cavitamuralis' ) adapted to microfistulous niches in CD. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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