The gut-brain axis in Alzheimer's and Parkinson's diseases: a comparative perspective

Global health challenges associated with neurodegenerative disorders are increasing, prompting growing interest in the gut-brain axis (GBA) as a key contributor to disease pathogenesis. The GBA represents a bidirectional communication network linking the gut microbiota, immune signalling pathways, metabolic processes, and the central nervous system (CNS). This review highlights the role of the GBA in the onset and progression of Alzheimer's disease (AD) and Parkinson's disease (PD), focusing on comparative disease mechanisms involving microbial dysbiosis, neuroinflammation, and metabolic dysfunction. Particular emphasis is placed on alterations in short-chain fatty acids (SCFAs), lipopolysaccharide (LPS), microbial amyloids, and inflammatory mediators including tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB), and NLR family pyrin domain containing 3 (NLRP3) inflammasome, which contribute to protein misfolding, blood-brain barrier disruption, and the accumulation of amyloid-β, hyperphosphorylated Tau, and α-synuclein. Furthermore, the review discusses recent advances in artificial intelligence (AI) and machine learning (ML) for integrating microbiome, clinical, neuroimaging, and multi-omics datasets to improve disease prediction, biomarker discovery, and patient stratification. AI approaches, including random forest, support vector machine, convolutional neural networks, and XGBoost, together with microbiome analysis platforms such as QIIME 2 and multi-omics integration tools including mixOmics and MOFA+, are highlighted for their potential in precision neurology. Collectively, integrating GBA biology with AI-driven analytics provides promising opportunities for early diagnosis, personalised therapeutic strategies, and precision medicine to address the growing burden of neurodegenerative disorders.