The Gut-Brain Axis and Neurodegenerative Diseases: From Mechanistic Pathways to Therapeutic Interventions.

Abstract

As the global population ages, the incidence of neurodegenerative diseases (NDDs) has increased. Neurodegenerative diseases have complex pathogenesis and currently lack fundamental treatment methods. The gut-brain axis (GBA) participates in the pathogenesis of NDDs through bidirectional communication between the gut microbiota and the central nervous system (CNS). This review systematically introduces the pathogenic characteristics of representative NDDs such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), as well as the association mechanisms between these diseases and GBA. The pathogenic characteristics of NDDs are closely related to changes in the composition of the gut microbiota and differences in gut microbiota metabolites (such as short-chain fatty acids (SCFAs), neurotransmitters, tryptophan metabolites, etc.). These changes influence the CNS through multiple pathways, including neuroendocrine, vagus nerve, and immune regulation, ultimately contributing to the onset and progression of the diseases. Furthermore, we have collected and summarized preclinical and clinical evidence from recent years regarding therapeutic interventions based on the GBA mechanism, including probiotics, prebiotics, and fecal microbiota transplantation (FMT). Nevertheless, major knowledge gaps remain, particularly regarding causality between gut microbiota changes and NDDs, the underlying molecular mechanisms, and the clinical efficacy of GBA-targeted therapies. This article aims to review the mechanisms of the interaction between the gut microbiota and the brain in neurodegenerative diseases, and based on the existing experimental evidence, provide theoretical basis and future development directions for future prevention and treatment strategies targeting GBA.