Analisi della funzionalità del microbiota umano nei diversi distretti corporei

The human microbiota is the collective term for the diverse and ever-changing community of microorganisms in many human body compartments, including the gastrointestinal (GIT), genitourinary, respiratory, and skin surfaces. Mainly, the gut and the vaginal microbiota are among the human-related microbial communities which have been the most investigated because of the high complexity and extreme heterogeneity of the microbial ecosystems that they retain. These ecosystems have co-evolved over decades to form a mutually beneficial relationship with the human host that benefits both parties. Since bacteria and human hosts have a constant molecular conversation that ultimately is responsible for the host’s health, huge efforts have been placed into understanding the microbial composition and the functions of the GIT and vaginal microbiomes. Recently, it has been shown that “omics” technologies involving genomics and various functional genomics approaches are crucial when investigating the composition and activities exploited by bacteria, including those colonizing the human gut and the vaginal environments. This Ph.D. thesis investigates the role of bacterial communities in the GIT and vaginal tract. Specifically, the main interest is in understanding the molecular mechanisms behind the health-promoting effects of Lactobacillus crispatus in the vaginal microbiota. Using omics approaches, this thesis aims to unravel the presence of L. crispatus in the human vaginal microbiomes and to assess its molecular interaction/s with other members, including various pathogenic microorganisms linked to vaginal infections. Additionally, this Ph.D. thesis explores the impact of amoxicillin-clavulanic acid (AMC), a commonly used antibiotic in pediatric care, on members of the Bifidobacterium genus, which represents one of the primary microbial colonizers of the human gut. Specifically, this thesis investigates AMC-resistant bifidobacteria and their role in preserving gut pg. 6 microbiota diversity during antibiotic treatment. In investigating the molecular basis of this resistance, studies were carried out on extracellular structures, such as exopolysaccharides (EPS), present on the surface of AMC-resistant strains. We have molecularly characterized these EPS structures through omics approaches, providing evidence about their crucial role in shielding the bacterial cell against AMC antibiotic. In the final section of this Ph.D. thesis, we have identified prototype strains for various Bifidobacterium species using in silico methodology based on an ecological and phylogenomic-driven approach. These potential candidates were tested in vitro to evaluate their interactions with the human host and other gut microbiota members, aiming to preserve or restore gut microbiota homeostasis.