Neurodegeneration and Gut Microbiota Pathophysiological Links and Therapeutic Opportunities

Abstract

The vagus nerve, sympathetic and parasympathetic fibres, and the hypothalamic–pituitary–adrenal (HPA) axis are among the neural, endocrine, and immune pathways that mediate the intricate bidirectional communication network known as the microbiota gut brain axis (MGBA), which connects the central nervous system (CNS) and the gastrointestinal tract.  Neurological diseases (NDs) like anxiety, depression, autism spectrum disorder, Parkinson's disease (PD), and Alzheimer's disease (AD) have been increasingly associated with dysbiosis, or changes in the makeup of the gut microbiota.  Dysbiosis affects the start and course of disease by causing neuroinflammation, microglial activation, compromised blood–brain barrier integrity, and the generation of neurotoxic metabolites.  In addition to producing neuroactive substances like short-chain fatty acids (SCFAs), which control behaviour, synaptic plasticity, and brain health, the gut microbiota also influences immunological function through chemokines and cytokines. Probiotics, prebiotics, symbiotic, dietary modification, and faecal microbiota transplantation are examples of emerging treatment approaches that target the MGBA and have the potential to improve cognitive performance, restore microbial balance, and lessen neuroinflammation in neurodegenerative diseases.  This review uses the terms "gut–brain axis," "microbiome dysbiosis," "neurodegeneration," "Alzheimer's disease," and "Parkinson's disease" to synthesise information from PubMed, Scopus, Ovid Medline, Cochrane Review, and Google Scholar up until July 2025.  The results emphasise the therapeutic potential of gut microbiota changes and emphasise their critical involvement in neurodevelopment, ageing, and neurodegeneration.  Clinical translation is still lacking, though, and more thorough, long-term human research is needed to clarify causal links, improve intervention techniques, and use the MGBA to treat neurodegenerative illnesses.