Background: Spondyloarthritis (SpA) comprises a group of chronic inflammatory rheumatic diseases frequently associated with extra-articular manifestations, particularly gastrointestinal involvement. Subclinical intestinal inflammation and alterations in gut microbiota composition have been described in SpA patients, even in the absence of overt inflammatory bowel disease (IBD), supporting the existence of a gut–joint axis. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are microbial metabolites produced through dietary fiber fermentation and play a central role in intestinal homeostasis and immune regulation. Among them, butyrate is essential for maintaining epithelial barrier integrity and modulating inflammatory responses. Although altered SCFA profiles have been reported in IBD and other inflammatory conditions, their role in SpA remains incompletely understood. Secretory immunoglobulin A (SIgA) is a key component of mucosal immunity, contributing to immune tolerance and host–microbiota interactions. Dysregulated IgA responses have been associated with chronic inflammation and autoimmune diseases; however, the relationship between SCFAs, SIgA, and disease activity in SpA has not been fully elucidated.

Objectives: To assess the association between fecal short-chain fatty acid levels, serum secretory IgA concentrations, and disease activity indices in patients with spondyloarthritis, with and without gastrointestinal symptoms, and to compare these parameters with patients with inflammatory bowel disease and healthy controls.

Methods: A total of 24 adults aged 18–65 years were included: 12 patients with SpA without IBD, 6 patients with IBD, and 6 healthy controls. Clinical assessment included evaluation of gastrointestinal symptoms and disease activity using validated indices. Serum secretory IgA levels were measured by ELISA, and fecal concentrations of acetate, propionate, and butyrate were quantified using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). Non-parametric statistical analyses were performed to compare groups and evaluate correlations. Ethics committee approval

Results: The study population was predominantly male, with the exception of the IBD group, in which males accounted for 33.3% of participants. Healthy controls had the lowest median age (32.5 years [IQR: 27.75–42.75]), whereas the highest median age was observed in SpA patients presenting gastrointestinal symptoms (40.0 years [IQR: 38.0–46.0]). Regarding nutritional status, the IBD group exhibited the lowest median body mass index (BMI), while the highest BMI values were recorded in SpA patients with gastrointestinal involvement. Healthy controls were characterized by negative fecal calprotectin results, normal total IgA levels, and low circulating SIgA concentrations. In contrast, SpA patients with gastrointestinal symptoms showed significantly elevated serum SIgA levels compared with healthy controls (p < 0.001). Consistent with the inflammatory nature of the disease, individuals with IBD exhibited increased SIgA levels, along with higher erythrocyte sedimentation rate and C-reactive protein values relative to healthy controls. Significant differences in fecal butyrate levels were observed among groups (p = 0.027). Markedly reduced butyrate and total SCFA concentrations were found in SpA patients with gastrointestinal symptoms and in IBD patients compared with healthy controls. Healthy controls and SpA patients without gastrointestinal symptoms exhibited significantly higher butyrate levels than the IBD group. No significant differences in fecal SCFA levels were detected between SpA patients with gastrointestinal symptoms and those with IBD. In SpA patients without gastrointestinal symptoms, fecal butyrate levels were inversely correlated with serum SIgA concentrations (CC = −0.90, p = 0.037) and positively correlated with disease activity indices, including ASDAS-CRP and BASDAI.

Conclusions: Fecal short-chain fatty acid profiles, particularly butyrate, are altered in SpA and are associated with mucosal immune markers and disease activity. The observed differences in butyrate levels and their correlations with serum SIgA and clinical indices support a relevant role of gut-derived microbial metabolites in SpA pathophysiology. These findings reinforce the concept of a gut–joint axis and suggest that SCFAs may represent potential biomarkers of immune dysregulation and disease activity. Further studies with larger cohorts are warranted to elucidate underlying mechanisms and explore therapeutic implications.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.