Genomic repertoires linked with pathogenic potency of arthritogenic <i>Prevotella copri</i> isolated from the gut of patients with rheumatoid arthritis.
basic_science · Level V
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- Record sourced from PubMed, PMID 36627170.
- Also identified by DOI 10.1136/ard-2022-222881 and PMC identifier 10176341.
- Licence recorded as CC BY-NC.
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Abstract
<i>Prevotella copri</i> is considered to be a contributing factor in rheumatoid arthritis (RA). However, in some non-Westernised countries, healthy individuals also harbour an abundance of <i>P. copri</i> in the intestine. This study investigated the pathogenicity of RA patient-derived <i>P. copri</i> (<i>P. copri</i> <sub>RA</sub>) compared with healthy control-derived <i>P. copri</i> (<i>P. copri</i> <sub>HC</sub>). We obtained 13 <i>P</i>. <i>copri</i> strains from the faeces of patients with RA and healthy controls. Following whole genome sequencing, the sequences of <i>P. copri</i> <sub>RA</sub> and <i>P. copri</i> <sub>HC</sub> were compared. To analyse the arthritis-inducing ability of <i>P. copri</i>, we examined two arthritis models (1) a collagen-induced arthritis model harbouring <i>P. copri</i> under specific-pathogen-free conditions and (2) an SKG mouse arthritis model under <i>P. copri</i>-monocolonised conditions. Finally, to evaluate the ability of <i>P. copri</i> to activate innate immune cells, we performed in vitro stimulation of bone marrow-derived dendritic cells (BMDCs) by <i>P. copri</i> <sub>RA</sub> and <i>P. copri</i> <sub>HC</sub>. Comparative genomic analysis revealed no apparent differences in the core gene contents between <i>P. copri</i> <sub>RA</sub> and <i>P. copri</i> <sub>HC</sub>, but pangenome analysis revealed the high genome plasticity of <i>P. copri</i>. We identified a <i>P. copri</i> <sub>RA</sub>-specific genomic region as a conjugative transposon. In both arthritis models, <i>P. copri</i> <sub>RA</sub>-induced more severe arthritis than <i>P. copri</i> <sub>HC</sub>. In vitro BMDC stimulation experiments revealed the upregulation of IL-17 and Th17-related cytokines (IL-6, IL-23) by <i>P. copri</i> <sub>RA</sub>. Our findings reveal the genetic diversity of <i>P. copri</i>, and the genomic signatures associated with strong arthritis-inducing ability of <i>P. copri</i> <sub>RA</sub>. Our study contributes towards elucidation of the complex pathogenesis of RA.
Medical subject headings
- Gastrointestinal Microbiome
- Arthritis, Rheumatoid