THE ROLE OF INTESTINAL MICROBIOTA IN CELIAC PATIENTS WITH PERSISTENT SYMPTOMS DESPITE THE GLUTEN-FREE DIET

Introduction: The intestinal microbiota plays a fundamental role in the functional homeostasis of the gastrointestinal tract and offers many benefits to the host through some physiological functions. Several studies suggest that it can contribute to the onset of symptoms of celiac disease and influence also the response to the gluten free diet (GFD). Celiac disease (CD) patients are characterized by a dysbiotic gut microbiota and it has been hypothesized it can favour the maintenance of the inflammatory state in patients that do not respond adequately to the GFD, resulting in a permanence of the symptoms. Aim of the study: This study aims to investigate the gut microbiota composition in patients with CD adhering to a GFD. The analysis distinguishes between responders and non-responders to the diet, who continue to experience persistent symptoms despite strict adherence for 6–12 months. Furthermore, it seeks to identify specific microbial profiles associated with the disease that may serve as potential biomarkers for diagnosis and monitoring in clinical practice. Materials and methods: Data were collected from 68 CD patients treated at the celiac disease clinic of the University Hospital of Padua. This population is composed of 49 responders and 19 non-responders to a GFD. The non-responders were further stratified based on the presence or absence of villous atrophy and positive lymphocytic infiltrate. After informed consent was obtained, samples of feces for the analysis of the microbiota were collected. Fecal samples were processed by BMR Genomics s.r.l., using sequencing of the V3–V4 hypervariable region of the 16S rRNA gene. The data included descriptive analysis of bacterial richness and diversity indices, reflecting microbiota biodiversity compared to a healthy reference population. The relative abundance levels of dominant bacterial phyla and the presence of potentially pathogenic bacteria were also evaluated and compared to healthy controls. ​ Conclusion: The findings of our analysis suggest that although alpha diversity appears restored in both responders and non-responders to the GFD, differences in specific bacterial taxa, such as increased Proteobacteria and reduced SCFA-producing bacteria in non-responders, may reflect ongoing mucosal inflammation. Potential sex-specific differences were highlighted, especially an enrichment of bacterial taxa in females. The results support a model in which both mucosal damage and GFD modulate the gut microbiota, which may in turn influence symptom persistence. Overall, causality still needs to be established. The small sample size limits the analysis and future studies, including metabolomic analyses, could be useful to better clarify microbiota–host interactions in non-responsive CD.