Phd in EXPERIMENTAL AND CLINICAL HEPATO-GASTROENTEROLOGY

Thesis title: L’impatto degli interventi nutrizionali sugli outcome di malattia nelle patologie con alterata permeabilità intestinale

Background: Irritable bowel syndrome (IBS) is one of the most common disorders of gut–brain interaction (DGBI), and it is associated with fibromyalgia (FM) in up to 65% of cases. The pathophysiology of IBS involves dysfunction of the gut–brain axis and peripheral factors, including alterations in the gut microbiota, impairment of the mucosal barrier, and activation of the immune system. For FM, a dysfunction of the gut–musculoskeletal axis has been recently proposed. Nutritional interventions such as the low FODMAP diet (LFD) have been suggested as therapeutic strategies for the management of both IBS and FM. Aims:To evaluate the clinical effect of the LFD on IBS and FM symptoms, quality of life (QoL), and serological markers of intestinal permeability (zonulin – ZO; lipopolysaccharide – LPS) in patients with IBS, FM, and FM+IBS. Methods:This was a prospective study involving 39 patients divided into three groups (IBS, FM, FM+IBS). The dietary protocol included a 4-week restriction phase, an 8-week reintroduction phase, and a 6-month follow-up with a personalized diet. Clinical data, body composition, QoL (SF-36), disease-specific scores (IBS-SSS, FIQ, PDS, CSI), and intestinal permeability markers were collected at four time points (T0, T1, T2, T3). Results: The LFD led to a significant improvement in IBS symptoms after just one month, particularly in patients with isolated IBS (–101.1, p < 0.001), while in FM+IBS patients the effect was more gradual but sustained up to 6 months. QoL significantly improved over time across all groups, especially in FM+IBS patients, with clinically relevant increases in physical functioning (+36.2%) and emotional well-being (+46.4%). Regarding intestinal permeability markers, ZO significantly decreased only in the FM+IBS group after the restriction phase (T1), but subsequently increased. LPS levels did not show significant changes over time, though a trend toward higher values was observed, particularly in FM groups. A significant correlation between delta ZO and LPS was found only in the IBS group (β = 0.052, p = 0.03), suggesting different pathogenic mechanisms across subgroups. Conclusions: The low FODMAP diet proved effective in improving clinical symptoms and quality of life in patients with IBS and FM, particularly in those with comorbidity. However, its effects on intestinal permeability appear partial and transient, suggesting the need for longer-term or personalized nutritional strategies to maintain gut barrier integrity, especially in FM patients.