Research Article: Metagenomic characterization of gut microbiota in rheumatoid arthritis-associated interstitial lung disease: taxonomic shifts and clinical correlations
Abstract:
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation with limited diagnostic biomarkers. While gut microbiota dysbiosis contributes to rheumatoid arthritis (RA) pathogenesis, its specific role in RA-ILD remains poorly characterized.
We performed shotgun metagenomic sequencing on fecal samples from 41 participants: 10 RA-ILD patients, 20 RA patients without ILD (RA-non-ILD), and 11 healthy controls (HCs). We assessed alpha and beta diversity, differential abundance (Wilcoxon rank-sum tests with FDR correction), Spearman correlations with clinical parameters, microbial co-occurrence networks, and random forest classification.
Alpha and beta diversity did not differ significantly among groups. After FDR correction, no genus differed significantly between RA-ILD and RA-non-ILD. Exploratory analysis (uncorrected P < 0.05) revealed enrichment of Escherichia/Shigella in RA-ILD (11.72% vs. 2.66%, P = 0.003) and depletion of Roseburia (1.05% vs. 3.77%, P = 0.005) and Ruminococcus (5.98% vs. 7.85%, P = 0.032), while Faecalibacterium showed a trend toward depletion without reaching nominal significance (4.45% vs. 4.66%, P = 0.409). Correlation analysis revealed a dichotomous pattern: pro-inflammatory genera correlated positively with disease activity, while butyrate-producing genera correlated negatively. Co-occurrence network analysis showed RA patients had a more complex network than HC and RA-ILD. Random forest classification identified Bifidobacterium , unclassified_ Oscillospiraceae, and unclassified_Lachnospiraceae as top discriminators between HC and RA, and unclassified_ Bacteroidaceae, Parabacteroides , and Blautia for RA-ILD vs RA.
RA-ILD is associated with specific gut microbial alterations—notably Escherichia/Shigella enrichment and depletion of Roseburia and Ruminococcus —despite preserved overall diversity. These changes correlate with systemic inflammation and suggest a role for the gut microbiota in RA-ILD pathogenesis via the gut-lung axis. The identified taxa warrant validation as candidate biomarkers in larger cohorts.
Introduction:
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation with limited diagnostic biomarkers. While gut microbiota dysbiosis contributes to rheumatoid arthritis (RA) pathogenesis, its specific role in RA-ILD remains poorly characterized.
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