Background/Purpose: Fatigue affects 70% of primary Sjögren’s syndrome (pSS) patients, but its mechanisms remain unclear. We investigated clinical predictors and gut microbiota associations in pSS-related fatigue.

Methods: 196 pSS patients were stratified by ESSPRI and Profile of Fatigue (ProF) scores. Univariate/multivariable logistic regression identified fatigue predictors. Fecal samples from 57 patients underwent 16S rRNA sequencing.

Results: 1．ESSPRI fatigue dimension: Fatigue was associated with SAS (OR = 1.06, 95% CI: 1.01–1.12, p = 0.032) and IFN-γ (OR = 1.72, 95% CI: 1.34–2.2, p < 0.001). Fatigue improvement was linked to the use of total glucosides of paeony (OR = 1.98, 95% CI: 1.03–3.81, p = 0.041) and IgG levels (OR = 0.94, 95% CI: 0.90–0.99, p = 0.014).2．Profile of Fatigue-Somatic Dimension: Fatigue was associated with SAS (OR = 1.10, 95% CI: 1.04–1.16, p < 0.001), IFN-γ (OR = 1.37, 95% CI: 1.12–1.68, p = 0.003), and anti-SSB antibodies (OR = 2.72, 95% CI: 1.39–5.69, p = 0.008). Fatigue improvement correlated with total glucosides of paeony use (OR=2.32, 95%CI 1.07 ~ 5.01, p=0.032) and CH50 levels (OR=1.06, 95%CI 1.03-1.10, p＜0.001).3．Profile of Fatigue-Mental Dimension: Fatigue was associated with SAS (OR = 1.06, 95% CI: 1.01–1.11, p = 0.019) and SDS (OR = 1.05, 95% CI: 1.01–1.09, p = 0.016). Fatigue improvement was linked to male sex (OR = 0.10, 95% CI: 0.01–0.85, p = 0.035), hematologic involvement (OR = 0.44, 95% CI: 0.21–0.92, p = 0.029), CH50 (OR = 1.04, 95% CI: 1.01–1.07, p = 0.019), and anti-SSB antibody positivity (OR = 0.45, 95% CI: 0.21–0.95, p = 0.036).4．16S rRNA sequencing revealed significant differences in α- and β-diversity of gut microbiota between fatigue and non-fatigue groups. Escherichia-Shigella and Streptococcus were significantly enriched in the fatigue group, and their abundances showed a strong positive correlation with fatigue severity scores. In contrast, Ruminococcus torques group, Faecalibacterium, and Subdoligranulum were predominantly enriched in the non-fatigue group, with their abundances negatively correlated with fatigue scores.

Conclusion: This study, through a multi-dimensional assessment framework encompassing the ESSPRI fatigue dimension and the ProF physical/mental fatigue subscales, revealed that SAS, SDS, IFN-γ, and anti-SSB antibodies are associated with pSS-related fatigue. Total glucosides of paeony use, IgG levels, CH50 levels, sex(male), anti-SSB antibody status, and hematologic involvement significantly influence fatigue improvement in pSS patients. Gut microbiota may contribute to the pathogenesis of pSS-related fatigue. These findings provide critical insights into the mechanisms underlying pSS-related fatigue and suggest novel strategies for diagnosis and therapeutic intervention.

Binary logistic regression based on Profile of Fatigue-Somatic improvement grouping

Binary logistic regression based on Profile of Fatigue-Mental improvement grouping

LEfSe analysis of gut microbiota between two groups

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gut-microbiota-dysbiosis-and-clinical-predictors-of-fatigue-in-primary-sjogrens-syndrome-a-multi-omics-study/