The Impacts of Gluten-free Diet in Patients With Ankylosing Spondylitis

Ankylosing Spondylitis (AS) is a chronic, progressive, inflammatory rheumatic disease that severely impairs patients' quality of life and functional capacity. The gut-joint axis theory in the pathogenesis of AS is gaining increasing support. Specifically, the increase in intestinal permeability mediated by zonulin, and the subsequent leakage of bacterial products (e.g., LPS) into the circulation, is recognized as a central mechanism in many diseases, including AS. Gluten has been proven to be one of the most potent dietary triggers of zonulin release, independent of genetic predisposition. Despite this, the clinical effects of a gluten-free diet (GFD) on this specific mechanism and its potential in AS patients have not yet been fully elucidated. Although indirect evidence suggesting that a GFD may provide clinical improvement in AS patients is accumulating, there are no studies in the literature that directly test the underlying biological mechanism (zonulin → LPS → systemic inflammation). This represents a critical knowledge gap that prevents clinicians from providing evidence-based dietary recommendations to patients. Therefore, investigators basically propose two hypotheses.

Hypothesis 1: An 8-week gluten-free diet in patients with Ankylosing Spondylitis will improve intestinal barrier integrity by reducing gliadin-induced zonulin release.

Hypothesis 2: The reduction in intestinal permeability will decrease the amount of lipopolysaccharide (LPS) translocating into the circulation and the subsequent pro-inflammatory cytokine response (TNF-α, IL-6). Consequently, this mechanism will lead to a measurable clinical improvement in disease activity (BASDAI) and quality of life (ASQoL).

To this end, an 8-week, randomized controlled prospective intervention study has been designed, which will include 60 AS patients aged 18-64. The intervention group (Gluten-Free Diet Group, n=30) will follow a gluten-free diet for 8 weeks in addition to their current treatments. The daily energy requirement for patients in this group will be calculated (using the Harris-Benedict equation for basal metabolic rate, adjusted for physical activity levels), and a gluten-free diet will be planned accordingly. In the initial face-to-face meeting, a dietitian will explain how to properly adhere to participants the gluten-free diet.Compliance will be monitored by the dietitian at weeks 2, 4, and 6 using a 1-day food record. Patients who do not adhere to the gluten-free diet will be excluded from the study. The control group (n=30) will continue with their current standard clinical follow-up without any dietary intervention. Disease activity, functional status, gastrointestinal symptoms, and quality of life will be assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Gastrointestinal Symptom Rating Scale (GSRS), and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. All biochemical measurements will be performed at baseline and at the end of the 8th week. This design will allow us to evaluate whether a GFD provides an additional benefit to standard care in real-world clinical practice.

The primary objective of the study is to measure the effect of a GFD on markers of intestinal permeability (serum zonulin) and microbial translocation (serum LPS). The secondary objectives are to evaluate the reflections of this mechanistic change on systemic inflammation markers (CRP, TNF-α, IL-6) and clinical disease activity scores (BASDAI, ASQoL). Measurements will be performed using validated ELISA methods and standard clinical questionnaires.

The primary novelty of this project is that it will be one of the first studies to explain the efficacy of a GFD in AS patients by targeting the underlying biological mechanism (zonulin → LPS → inflammation). The findings obtained at the end of the project will contribute to the development of evidence-based dietary recommendations for the management of AS.

• effects of a 8 week Gluten Free Diet versus placebo diet on the activity of Ankylosing Spondylitis evaluated by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). [Time frame: Change from baseline BASDAI score at 8 weeks]
• effects of a 8-week Gluten Free Diet versus placebo diet on functional disability asssessed by Bath Ankylosing Spondylitis Functionnal Index (BASFI) questionnaire [Time frame: Change from baseline BASFI score at 8 weeks]
• effects of a 8 week Gluten Free Diet versus placebo diet on the quality of life of Ankylosing Spondylitis evaluated by the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL). [Time frame: Change from baseline ASQoL score at 8 weeks]
• effects of a 8-week Gluten Free Diet versus placebo diet on CRP levels [Time frame: Change from baseline CRP at 8 weeks]
• effects of a 8-week Gluten Free Diet versus placebo diet on ESR levels [Time frame: Change from baseline ESR at 8 weeks]
• effects of a 8 week gluten free diet versus placebo diet on the gastrointestinal symptoms [Time frame: Change from baseline GSRS score at 8 weeks]
• change in body weight [Time frame: Change from baseline body weight at 8 weeks]
• change in Body Mass Index [Time frame: Change from baseline BMI at 8 weeks]
• effects of a 8-week Gluten Free Diet versus placebo diet on fasting glucose levels [Time frame: Change from baseline fasting glucose at 8 weeks]
• effects of a 8-week Gluten Free Diet versus placebo diet on fasting insulin levels [Time frame: Change from baseline fasting insulin at 8 weeks]
• effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum calprotectin levels [Time frame: Change from baseline serum calprotektin at 8 weeks]
• effects of a 8-week Gluten Free Diet versus placebo diet on fasting serum haptoglobin levels [Time frame: Change from baseline serum haptoglobin at 8 weeks]