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.
