A recent study published in Arthritis Research & Therapy has highlighted a compelling association between gut inflammation and structural spinal damage in patients with axial spondyloarthritis (axSpA), independent of other established risk factors for radiographic progression. While genetic, immune, and environmental factors are known contributors to the disease pathogenesis, emerging evidence indicates that intestinal inflammation and alterations in gut microbiota may play a pivotal role in disease progression through the gut–joint axis.
The Swedish study examined 228 patients with well-characterized axSpA (76 with non-radiographic and 152 with radiographic disease) enrolled in a population-based cohort in southern Sweden. Structural spinal damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), a validated tool for quantifying new bone formation and spinal changes over time. Gut inflammation was measured using fecal calprotectin (F-calprotectin), a noninvasive biomarker of intestinal inflammation derived from neutrophil activation. Patients were stratified into three groups based on F-calprotectin concentrations: normal (<50 mg/kg), moderately elevated (50–149 mg/kg), and distinctly elevated (≥150 mg/kg), representing no, mild, and evident gut inflammation, respectively.
The analysis revealed a clear gradient between gut inflammation and structural spinal damage. Patients with higher F-calprotectin levels had significantly greater mSASSS scores, indicating more pronounced spinal changes. In both the overall axSpA cohort and the subgroup with radiographic axSpA, the differences in spinal damage across the F-calprotectin categories were statistically significant. Individuals with elevated F-calprotectin (≥50 mg/kg) were more likely to have mSASSS values above the median, with an adjusted odds ratio (OR) of 2.2 (95% CI 1.1–4.2) for the entire cohort and 2.9 (95% CI 1.2–7.1) for those with radiographic disease. These associations persisted even after adjusting for key variables such as sex, symptom duration, HLA-B27 positivity, smoking status, C-reactive protein (CRP) levels, and treatment with NSAIDs or anti-TNF therapy, underscoring that gut inflammation may independently drive structural progression in axSpA.
The findings strong support the hypothesis that subclinical gut inflammation is not merely a comorbid feature but may have a pathogenic role in bone remodeling and ankylosis. Prior endoscopic and histopathological studies have reported microscopic gut inflammation in up to 60% of patients with spondyloarthritis, even in the absence of gastrointestinal symptoms. This intestinal inflammation is thought to trigger immune activation via microbial dysbiosis and mucosal barrier dysfunction, promoting systemic inflammation and osteoproliferation through pathways involving interleukin (IL)-23, IL-17, and tumor necrosis factor (TNF).
Complementing this finding, a related study by Sagard et al. demonstrated that gut dysbiosis, defined by an altered microbial composition, was significantly more prevalent in ankylosing spondylitis and associated with worse clinical outcomes. Using fecal 16S rRNA sequencing and the GA-map™ Dysbiosis Test, dysbiosis (score ≥3) was identified in 36% of AS patients, compared with 25% in non-radiographic axSpA and 17% in healthy controls. Patients with dysbiosis exhibited higher disease activity (ASDAS-CRP +0.6; BASDAI +1.6), poorer functional status (BASFI +1.5), and higher physician-assessed disease activity, even after controlling for confounders such as age, sex, medication use, and gut inflammation. These findings point to a pathogenic link between microbial imbalance and disease severity, suggesting that both gut inflammation and dysbiosis may synergistically influence disease mechanisms.
These studies reinforce the concept of the gut–joint axis as a critical interface in axial spondyloarthritis, where intestinal inflammation and microbial alterations contribute to systemic immune activation and skeletal remodeling. They also highlight the importance of considering gut health in disease monitoring and management. The researchers emphasize that further longitudinal studies are needed to clarify the temporal and causal relationships between gut inflammation and spinal damage. Such insights could pave the way for novel therapeutic strategies targeting intestinal inflammation and microbial composition to slow or prevent structural progression in axSpA.
References
- Wallman JK, Mogard E, Sagard J, Andréasson K, Marsal J, Inci F, Geijer M, Olofsson T, Lindqvist E. Gut inflammation is associated with structural spinal damage in axial spondyloarthritis – results from the observational SPARTAKUS cohort. Arthritis Res Ther. 2025 Oct 21;27(1):195.
- Sagard J, Olofsson T, Mogard E, Marsal J, Andréasson K, Geijer M, Kristensen LE, Lindqvist E, Wallman JK. Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis. Arthritis Res Ther. 2022 Feb 12;24(1):42.