Petrella, Lidia (2025) Bioactive food components as modulators of mitochondrial function in autism spectrum disorders. [Tesi di dottorato]

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Abstract

Autism Spectrum Disorders (ASD) are complex and heterogeneous neurodevelopmental conditions characterized by deficits in social communication and restricted behavioral patterns. Beyond their neurological features, ASD are increasingly associated with systemic metabolic disturbances, immune dysregulation, and mitochondrial dysfunction. In this context, the gut–liver–brain axis has gained relevance as a key interface linking gut microbiota composition, hepatic metabolism, and neural function, with gut dysbiosis and intestinal barrier disruption contributing to systemic inflammation and altered bioenergetics. Metabolic abnormalities and nutritional imbalances—frequently driven by atypical eating behaviors and restricted diets—further exacerbate oxidative stress, mitochondrial dysfunction, and inflammatory state, especially in the most metabolically active organs such as the liver and brain. These alterations form a pathogenic network that may influence both behavioral outcomes and the progression of comorbidities commonly observed in ASD. This PhD thesis aimed to explore the role of bioactive food components in modulating mitochondrial function within the context of ASD-related metabolic and inflammatory alterations. Using the BTBR mouse model, we identified marked hepatic and synaptic mitochondrial dysfunction, redox imbalance, and gut microbiota shift, supporting an altered gut–liver–brain axis. Nutritional supplementation with dimethylglycine and B-group vitamins, by modulating gut microbial composition, improved inflammatory and metabolic state, partially restored mitochondrial efficiency in both liver and brain, ameliorating ASD-like behaviors. Overall, these findings underscore the relevance of metabolic and nutritional factors in ASD pathophysiology and highlight the potential of mitochondria-targeted dietary strategies as complementary approaches to improve systemic and neurobiological outcomes.

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