Seasonal climate variation, gut microbiota dysbiosis, and rheumatoid arthritis disease activity: A cross-sectional analysis of the gut–joint axis
Keywords:
climate variation, dysbiosis, faecal biomarkers, gut microbiota, rheumatoid arthritisAbstract
Background: Seasonal environmental variation has been associated with fluctuations in rheumatoid arthritis (RA) disease activity, but the biological mechanisms underlying these changes remain unclear. Increasing evidence suggests that the gut-joint axis may mediate environmental effects on systemic inflammation. This study investigated whether seasonal environmental variation is associated with changes in gut inflammatory biomarkers, microbiota diversity, and RA disease activity.
Methods: A cross-sectional study was conducted among 1,080 patients with RA diagnosed according to the 2010 ACR/EULAR criteria. Participants were stratified by season into Winter (n=225), Pre-Monsoon (n=315), Monsoon (n=360), and Post-Monsoon (n=180). Climate parameters, serological markers (RF and anti-CCP), gut microbiota diversity (16S rRNA sequencing), inflammatory biomarkers (calprotectin and lactoferrin), disease activity indices (DAS28-CRP and CDAI), and patient-reported outcomes were assessed.
Results: Serological markers showed no seasonal variation. In contrast, disease activity indices, gastrointestinal symptoms, and faecal inflammatory biomarkers varied significantly across seasons (all P<0.001), with the highest levels observed during Pre-Monsoon and Monsoon periods. Faecal lactoferrin demonstrated strong positive associations with disease activity and functional disability (adjusted β=0.75, R² 0.71), values markedly exceeding the predictive capacity of conventional serological markers (adjusted R² 0.12).
Conclusion: Seasonal environmental variation is linked to changes in RA disease activity and intestinal inflammation. These findings support a climate-gut-inflammation pathway in which environmental stressors may influence RA manifestations via intestinal dysbiosis and gut-mediated inflammatory mechanisms. As this study was cross-sectional, these findings are hypothesis-generating and do not establish causal or temporal relationships; longitudinal studies are required to confirm.
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