Metagenomic characterization of gut microbiota in rheumatoid arthritis-associated interstitial lung disease: taxonomic shifts and clinical correlations.

The association between “unclassified_Bacteria” and RF positivity was nominally significant (Mann-Whitney U test, P = 0.022, Supplementary Table 5 ), though it did not remain significant after FDR correction ( q = 0.391).

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Faecalibacterium showed significant negative correlations with DAS28-CRP (ρ= -0.37, P = 0.044) and a strong trend with DAS28-ESR (ρ=-0.34, P = 0.070).

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In pairwise comparisons, the separation between RA-ILD and RA-non-ILD groups showed a trend toward significance but did not reach the conventional threshold (R2 = 0.062, P = 0.095).

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7.85%, P = 0.032), while Faecalibacterium showed a trend toward depletion without reaching nominal significance (4.45% vs. 4.66%, P = 0.409).

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Intriguingly, a group of unclassified bacteria, designated as “unclassified_Bacteria,” displayed the broadest and strongest positive correlations across nearly all inflammatory and disease activity measures, reaching statistical significance with CRP (ρ = 0.44, P = 0.015) and showing a notable trend with RF positivity (see below).

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However, likely due to the limited number of seronegative individuals in our cohort (n=5-6), most of these associations did not reach statistical significance after multiple testing correction.

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The strong correlation between Escherichia/Shigella abundance and DAS28-ESR, which remained as a significant trend, suggests that this organism may contribute meaningfully to the systemic inflammatory burden in RA-ILD patients.

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