Bacterial translocation and intestinal permeability in early axial spondyloarthritis association with 5-year outcomes: insights from the DESIR cohort

OBJECTIVES: To evaluate the association between initial serological markers of intestinal permeability (IP) and bacterial translocation (BT), and the development of extra-musculoskeletal manifestations (EMM) and radiographic progression in axial spondyloarthritis (axSpA). METHODS: Serum samples from axSpA patients included in the DESIR cohort with clinical data available at 5 years were analyzed. Gut permeability was assessed by zonulin levels and BT was assessed by lipopolysaccharide (LPS)-derived 3-hydroxymyristate and phospholipid transferase protein (PLTP) levels. The associations of baseline serological markers with the presence of EMM and imaging sacroiliac scores were analyzed both at baseline and as primary outcomes of disease progression after 5 years follow-up. Associations were tested using univariate and multivariate logistic regression analyses. RESULTS: A total of 297 patients were included (mean age 31.5 ± 7.4 years; 48.5% female; 88.9% HLA-B27 positive). Baseline levels of 3-hydroxymyristate, PLTP activity, and zonulin showed no association with the presence or incidence of EMM. Baseline zonulin levels were lower in patients with baseline radiographic sacroiliitis (88.1 ng/ml vs. 140.6 ng/ml, p < 0.001), though this was not confirmed in multivariate linear regression. PLTP activity was positively correlated with the baseline SPARCC sacroiliac joint score (β = 0.61, p = 0.02), and this association remained significant after adjusting for age, sex, and CRP (β = 0.58, p = 0.03). Moreover, PLTP activity was significantly higher in patients with radiographic sacroiliitis progression (6.1 vs. 5.2 nmol/h/ml, p = 0.02), an effect maintained after adjustment (β = 0.27, p = 0.02). CONCLUSION: PLTP activity is a promising biomarker associated with sacroiliac joint inflammation and radiographic progression over 5 years in recent axSpA.