ETD

• diabete
• epigenetic
• epigenetica
• malattie metaboliche
• metabolic desease
• microbiome
• microbiota
• obesità

Metabolic diseases (hypertension, type 2 diabetes, hyperlipidaemia, obesity and non-alcoholic fatty liver disease) are a major public-health priority because they often coexist as metabolic syndrome, increasing the risk of chronic complications, cardiovascular disease, cancer and premature mortality. Global Burden of Disease data (2000–2019) show a steady rise in deaths and prevalence, with substantial economic consequences both in high-income countries (healthcare expenditure) and in middle- and low-income settings (a drag on development). In this context, the gut microbiota has emerged as a key player: dysbiosis is associated with obesity, diabetes and NAFLD and may contribute causally by modulating energy metabolism, insulin sensitivity and inflammation. The microbiota—highly variable between individuals yet relatively stable within the same person—produces metabolites such as SCFAs that interact with nutrient-sensing pathways (IIS/FOXO and mTOR) and intestinal receptors (GPR41/43/109A), thereby influencing immunity, blood pressure and gut-barrier integrity. Dysbiosis may also affect the gut–brain axis through neurotransmitters, endotoxaemia and neuroinflammation. An additional regulatory layer is epigenetics: microbial metabolites and dietary methyl donors (folate, choline, B12, betaine, SCFAs) modulate ncRNAs, DNA methylation and histone modifications, with potential implications for metabolic and oncological conditions. The aim of this thesis is to analyse the microbiota–epigenome interplay in obesity, diabetes and NAFLD and to evaluate its preventive and therapeutic implications (diet, pre/pro/postbiotics, nutraceuticals, antibiotics, microbiota transplantation).