Phd in INNOVATIVE BIOMEDICAL TECHNOLOGIES IN CLINICAL MEDICINE

Thesis title: HORIZONTAL MICROBIAL STRAIN TRANSMISSION BETWEEN COHABITANTS AND ITS ASSOCIATION WITH THE RISK OF CELIAC DISEASE DEVELOPMENT

Background: Coeliac disease is an autoimmune disorder, primarily triggered by gluten ingestion and the presence of susceptibility genes (HLA DQ2/8). Despite 40% of the population carrying the genetic predisposition, only 2-5% develop the disease. The role of the gut microbiota has emerged as a potential “missing piece of the puzzle” in this discrepancy. Objective: Primary aim is to compare the rate of microbial strain sharing between two types of cohabiting related couples: (1) both individuals with celiac disease, and (2) one individual with celiac disease and the other healthy but genetically predisposed. Secondary objectives include characterizing the fecal and salivary microbiota profiles of celiac patients and healthy, genetically predisposed individuals. Methodology: A cross-sectional, case-control pilot study was conducted at Policlinico Gemelli and Policlinico Umberto I Hospitals. Participants were enrolled in a 1:2 ratio for cases (cohabiting relatives, both diagnosed with celiac disease) and controls (cohabiting relatives, one with celiac disease and one healthy but genetically predisposed). Demographical and clinical data were acquired. Fecal and salivary samples were collected from all participants for microbiome profiling using shotgun metagenomics. Results: A total of 61 cohabiting couples were enrolled, comprising 20 cases and 41 controls, matched for, gender, age, diet and BMI. No significant difference in microbial strain transmission between cases and controls was observed based on the Jaccard Index (p > 0.05). Alpha diversity profiling revealed no significant differences in fecal microbiota diversity between celiac and non-celiac individuals (p = 0.40181). However, beta diversity analysis showed a significant difference in overall microbial community composition between celiac and non-celiacs (p = 0.006). LEfSe analysis at the phylum level indicated that Bacteroidota was significantly more abundant in celiac patients (LDA score = -4.67, p = 0.002), whereas Actinobacteria and Firmicutes were more prevalent in non-celiac individuals (LDA scores = 3.93 and 4.53, respectively, p < 0.05). Conclusion: The familial clustering of celiac disease doesn’t appear to be explainable by increased microbial strain transmission between cohabitants. However, differences in intestinal microbiota composition between celiac and non-celiac individuals suggest that the gut microbiome may play a crucial role in disease pathogenesis.