GUT MICROBIOTA MODULATION BY DIET AND EXERCISE: EFFECTS IN THE PREVENTION OF NON-COMMUNICABLE DEGENERATIVE DISEASES AND IMPROVEMENT OF QUALITY OF LIFE

The gut microbiota (GM) is a central regulator of host homeostasis, influencing metabolic, immune, and neuroendocrine signaling. Dysbiosis has been implicated in the onset and progression of neurodegenerative and oncological diseases. This doctoral research examined microbiota–host interactions across three complementary clinical and experimental models. In the first study, GM composition was characterized in 109 patients with Parkinson’s disease (PD), clinically stratified by disease severity and presence of motor fluctuations. Disease progression was associated with a depletion of butyrate-producing taxa (e.g., Faecalibacterium, Roseburia) and an enrichment of mucolytic and pro-inflammatory genera (e.g., Alistipes, Collinsella, Desulfovibrio). Patients experiencing motor fluctuations exhibited a distinct dysbiotic profile, suggesting that microbial metabolic imbalance may contribute to impaired intestinal barrier function, systemic inflammation, and dopaminergic instability along the gut–brain axis. The second project investigated a 12-week home-based Mediterranean diet and aerobic exercise intervention in breast cancer survivors (n = 20). In addition to improvements in cardiometabolic biomarkers, GM analysis demonstrated a reduction in Proteobacteria—often linked to inflammation—and positive associations between Mediterranean diet adherence and butyrate-producing genera. These findings indicate that lifestyle modification can promote a microbiota configuration associated with improved metabolic and inflammatory status during survivorship. The third study explored microbiota-derived metabolites as modulators of tumor cell plasticity in non-small cell lung cancer (NSCLC). Propionate-rich supernatants from Acidopropionibacterium microaerophilum decreased ZEB1 and Vimentin expression while increasing E-cadherin in A549 cells, indicating inhibition of epithelial-to-mesenchymal transition (EMT). This supports a role for microbial metabolites in modulating tumor behavior through metabolic–epigenetic pathways. Across neurological and oncological contexts, the GM emerges as both a biomarker of disease state and a tractable therapeutic target. Strategies that reshape microbial composition or exploit microbial metabolite production may provide innovative avenues to mitigate neuroinflammation, enhance metabolic recovery after cancer therapy, and limit tumor progression.