Casaburi, Giorgio (2014) Next generation genomic sequencing and bioinformatics approaches for the study of the human gut microbiome in selected diseases of the human gut. [Tesi di dottorato]

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Abstract

The advent of next generation sequencing technologies (NGS) has deeply transformed today’s biology. Thanks to this new approach, many areas of study have been developed and scientists have the ability to analyze nucleic acids of any biological entity. Metagenomics is one of the most recent and promising fields among NGS applications. It allows microbial community analysis within a specific environment in order to obtain knowledge on genomes and taxonomic composition of environmental microbes and entire microbial communities. In this context, the human microbiota, represented by the total ecological community of commensal, symbiotic, and pathogenic microorganisms coexisting in our bodies (Lederberg J; Scientist. 2001;15:8), is drawing research’s attention as it plays a central role in maintaining healthy status or leading to disease conditions (Wang, Zi-Kai WJG. 2013:1541). Particularly, the human gut is colonized by thousands of different microbial species, of which several billions are bacteria involved in important functions: gut permeability, immune system development and activation, metabolic function and colonization resistance (Prakash S. Nature. 2012;231-241). Many evidences relate the role of the gut microbiome in common bowel inflammatory diseases and autoimmune disorders (Xavier R. J. Nature. 2007:427-434). Here, I present two distinct studies based on amplicon metagenomics analysis in Crohn’s disease and Celiac disease, using next generation sequencing techniques. The aim of the project is to deeply analyze the gut microbiome composition, from duodenal biopsies of Crohn’s disease and Celiac disease affected patients. The first study compares the microbiome bacterial composition of a child affected by Crohn’s disease before and after a nutritional therapy together with a matched healthy control. The second study pertains to the gut microbiome characterization (bacteria and fungi) in adults with active Celiac disease, compared with healthy controls and a group of non-active Celiac disease patients, following a gluten free diet. The goal is the identification of microbial signatures that could be related to the pathogenesis or contribute to the disease phenotype in both Crohn’s and Celiac disease.

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