Studio della modulazione del microbiota intestinale come potenziale approccio predittivo per la valutazione degli esiti clinici e stato di salute

Introduction and Aims: The intestinal microbiota, a complex ecosystem of microorganisms, plays an essential role in the metabolic, structural, and immune regulation of the human body. Alterations in its composition, known as intestinal dysbiosis, have been associated with numerous pathological conditions, including gastrointestinal, metabolic, and inflammatory diseases. This study focuses on the modulation of the intestinal microbiota as a potential tool to predict and improve clinical outcomes and health status. The study aims to explore the role of the intestinal microbiota in three specific contexts: (1) during the development of the first six months of a child's life; (2) the impact of nutritional counseling and probiotic supplementation in patients with Irritable Bowel Syndrome (IBS) and chronic constipation; and (3) the effect of Vedolizumab (VDZ) treatment on mucosal barrier integrity in patients with Inflammatory Bowel Diseases (IBD). Materials and Methods: Advanced gene sequencing techniques (16S rRNA) were used to characterize the intestinal microbiota in patient cohorts from the different study groups. Interventions included targeted nutritional counseling and dietary factor monitoring through the use of a 7-day food diary, FFQ, and MDSS. Gastrointestinal symptoms and therapeutic outcomes were evaluated using standardized questionnaires and clinical and endoscopic scores, such as the Partial Mayo Score, Harvey-Bradshaw Index, Mayo Endoscopic Sub-Score, and Simple Endoscopic Score. Intestinal permeability was assessed by measuring TEER (*cm²) and a fluorescent tracer (FD4) every 30 minutes for 120 minutes, ex vivo on mucosal tissues, using the Ussing Chambers system. Bioinformatic analysis was conducted to correlate microbiota changes with clinical and biological parameters across the study groups. Results: During the first 1,000 days of life, the microbiota composition is influenced by factors such as delivery mode, breastfeeding, and maternal diet, with long-term effects on health. Children born to mothers adhering to the Mediterranean diet (MD) demonstrated greater richness and diversity of probiotic bacterial OTUs, such as Faecalibacterium, Akkermansia, Bifidobacterium, Blautia, and Lachnospiraceae, compared to children whose mothers did not follow MD dietary recommendations during pregnancy and breastfeeding. In 47 IBS patients and 10 chronic constipation patients, dietary habit assessments did not show significant changes following nutritional counseling compared to 42 healthy volunteers. However, a significant improvement was observed in the abdominal pain intensity score in IBS patients at follow-up compared to baseline (p = 0.0135). Although strong correlations between intestinal microbiota and symptoms could not be identified, bacterial genera such as Prevotella and Bacteroides were identified as potential biomarkers for predicting clinical responses to GI symptoms following treatment. In IBD patients treated with Vedolizumab, significant improvements were observed in clinical and endoscopic scores (p<0.0001), promoting sustained clinical remission. Analyses conducted with the Ussing Chambers showed that VDZ contributes to restoring epithelial barrier integrity, with improved TEER values in IBD patients (p = 0.012). Enrichment of Bifidobacterium and Akkermansia in IBD patients was associated with clinical remission, suggesting that these bacterial taxa could reflect therapeutic responses to the drug and contribute to restoring intestinal health. Conclusion: The modulation of the intestinal microbiota represents an innovative approach to improving clinical outcomes and personalizing treatments in various pathological conditions. These findings highlight the importance of integrating microbiological, nutritional, and clinical data to promote a targeted therapeutic approach within the framework of personalized medicine