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Institute for Bioengineering of Catalonia (IBEC)
Title:Microbiota-gut-brain axis in the progression of cognitive disorders associated with Alzheimer's disease
Alzheimer's disease (AD) is one of the major global health challenges, with no effective treatments. Epidemiological studies indicate that AD has a long prodromal phase starting 15–20 years before clinical symptoms appear. Alterations in gut microbiota composition have been observed in AD patients, and these changes may influence neuroinflammation and contribute to early disease progression. This study proposes an integrated approach using humanized murine models (APP/PS1 transgenic mice) and Drosophila melanogaster screening to better understand the role of microbiota in AD and develop targeted interventions. From a larger longitudinal study, 90 representative samples were selected, including healthy controls, AD patients, and individuals with mild cognitive impairment (MCI), of whom half developed AD over the three-year observation period (MCI-AD). Using shotgun metagenomic sequencing, we characterized the gut microbiota composition. In parallel, metabolomics analysis allowed us to evaluate key metabolites involved in gut-brain communication, such as short-chain fatty acids, bile acids, trimethylamine , tryptophan metabolites, lipids and one carbon metabolism, previously associated with cognitive decline and AD progression. The impact of different bacterial strains on disease progression was assessed in flies through multiple cognitive tests and histological analyses. In mice, fecal microbiota transplantation was performed using samples from healthy donors and individuals with MCI-AD to investigate the role of gut microbiota in cognitive decline. Additionally, the combined effect of microbiota modulation and probiotic supplementation was evaluated. To explore potential mechanisms, epigenetic analyses of the hippocampus were conducted to assess microbiota-driven changes in gene regulation associated with neurodegeneration.
Mirko Paparella completed his Master's Degree in Biology Science and Human Nutrition from Università Campus Bio-Medico di Roma in 2023. He is currently a researcher at the Genomics Unit of IBEC (Institute for Bioengineering of Catalonia) in collaboration with the Center for Omic Sciences at EURECAT. His research focuses on genomics, epigenetics, and the gut-microbiotabrain axis, particularly in Alzheimer's disease and antibiotic resistance.