Résumé
•We show that biomarkers of bacterial translocation (circulating bacterial DNA) and intestinal permeability (I-FABP) are significantly increased in recently diagnose rheumatoid arthritis patients.•We show decrease of coprococcus genus in recently diagnose rheumatoid arthritis patients with a targeted metagenomic approach.•We highlight increase of bacterial lipid metabolism and several host inflammatory proteins in recently diagnose rheumatoid arthritis patients with a metaproteomic approach.•We describe physiopathological mechanism (bacterial translocation from intestinal microbiota) potentially involved in systemic and secondarily local inflammation in rheumatoid arthritis patients.
The objective of this study was to investigate the link between gut microbiota (GM) dysbiosis, gut inflammation, and bacterial translocation (BT) in recently diagnosed rheumatoid arthritis (RA). This case-control, observational study prospectively recruited recently diagnosed (<12 months) RA patients and age-matched healthy controls (HC) from two French hospitals between July 2014 to March 2018. The primary objective was to investigate GM composition in each group using 16S rRNA sequencing and metaproteomics approaches. Three plasmatic BT markers (sCD14, LPS-binding protein, and number of 16S rRNA gene copies) and one intestinal permeability marker (I-FABP) were quantified in blood samples.
Twenty-five were included in each group, and 50 stools and blood samples were analyzed. 16S rRNA gene analysis showed an decrease in Coprococcus in RA patients after Body Mass Index and HLA status. Circulating bacterial DNA (number of copies of the 16S rRNA gene) and plasmatic I-FABP were higher in RA patients compared to HCs (p < 0.01), indicating increased BT and intestinal permeability in these patients. Metaproteomics from stool samples highlighted an increased host humoral immune response in RA, with elevated levels of inflammatory proteins (azurocidin, cathepsin G, neutrophil defensing 1). Gut inflammation may contribute to increased intestinal permeability, leading to BT into the systemic circulation and thus chronic inflammation.
Summarized schematic illustration of the study. Among different exogenous factors (A), anti-inflammatory treatments and overweight could contribute to gut microbiota dysbiosis (B) favoring gut permeability (observed by the levels of I-FABP) (C), increased bacterial lipid metabolism (D) and local gut inflammation (E) . This early dysbiosis could contribute to BT in the systemic circulation (circularing bacterial DNA) and thus chronic inflammation (F). [Display omitted]