Gut microbiome and intestinal inflammation in preclinical stages of rheumatoid arthritis


Faecal Prevotellaceae, and other microbes, have been associated with rheumatoid arthritis (RA) and preclinical RA. The authors of this article, led by GCIR Prof. Axel Finckh, have performed a quantitative microbiome profiling study in preclinical stages of RA.

First-degree relatives of patients with RA (RA-FDRs) from the SCREEN-RA cohort were categorised into four groups: controls, healthy asymptomatic RA-FDRs; high genetic risk, asymptomatic RA-FDRs with two copies of the shared epitope; autoimmunity, asymptomatic RA-FDRs with RA-associated autoimmunity; and symptomatic, clinically suspect arthralgias or untreated new-onset RA.

Faecal samples were collected and frozen. 16S sequencing was performed, processed with DADA2 pipeline and Silva database. Cell counts (cytometry) and faecal calprotectin (enzyme-linked immunosorbent assay, ELISA) were also obtained. Microbial community analyses were conducted using non-parametric tests, such as permutational multivariate analysis of variance (PERMANOVA), Wilcoxon and Kruskal-Wallis, or Aldex2.

A total of 371 individuals were included and categorised according to their preclinical stage of the disease. Groups had similar age, gender and body mass index. The authors found no significant differences in the quantitative microbiome profiles by preclinical stages (PERMANOVA, R2=0.00798, p=0.56) and, in particular, no group differences in Prevotellaceae abundance. Results were similar when using relative microbiome profiling data (PERMANOVA, R2=0.0073, p=0.83) or Aldex2 on 16S sequence counts. Regarding faecal calprotectin, they found no differences between groups (p=0.3).

The authors could not identify microbiome profiles associated with preclinical stages of RA. Only in a subgroup of individuals with the most pronounced phenotypes did they modestly retrieve the previously reported associations.

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Why is it important?

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation, pain, and deformities. It results from environmental risk factors triggering autoimmunity in genetically vulnerable individuals. Recent research emphasizes mucosal health as a key factor in RA development. Intestinal inflammation and bacteria such as Prevotellaceae were thus linked to RA, especially in mouse models.

GCIR researchers studied Prevotellaceae and intestinal inflammation in 371 untreated first-degree relatives of RA patients at various preclinical stages. Surprisingly, contrary to murine models, they found no correlation between faecal microorganisms, intestinal inflammation, and preclinical RA stages.

These results challenge the generalizability of microbiome studies conducted from animal models of arthritis to humans, also emphasizing the limitations of relying on a single bacterium as a biomarker. Maybe future research should investigate the commonalities among the various microbes associated with RA, particularly in terms of gene function, surface antigens, and mucus-invading capabilities.

2 Feb 2024