The Gut-Brain Axis in Neurodegeneration: Mechanistic Insights and Emerging Therapeutic Perspectives

Harsha Marathe¹, Aarti Darade¹, Manoj Mahajan², Aman Upaganlawar³, Chandrashekhar Upasani⁴

Keywords: Gut-brain axis, gut microbiota, dysbiosis, neurodegenerative disorders, microbialmetabolites

DOI: 10.63475/yjm.v5i1.0295

DOI URL: https://doi.org/10.63475/yjm.v5i1.0295

Publish Date: 01-04-2026

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Author Affiliation:

1 Research Scholar, Department of Pharmacology, SNJB’s Shriman Sureshdada Jain College of Pharmacy, Neminagar, Chandwad, Nashik, India
2 Associate Professor, Department of Pharmacology, SNJB’s Shriman Sureshdada Jain College of Pharmacy, Neminagar, Chandwad, Nashik, India
3 Professor and Head, Department of Pharmacology, SNJB’s Shriman Sureshdada Jain College of Pharmacy, Neminagar, Chandwad, Nashik, India
4 Professor and Principal, Department of Pharmacology, SNJB’s Shriman Sureshdada Jain College of Pharmacy, Neminagar, Chandwad, Nashik, India

Abstract

The gut-brain axis (GBA) is an intricate, bidirectional communication network connecting the central nervous system (CNS) and gastrointestinal tract (GIT) via neural, immune, endocrine, and metabolic pathways. This dynamic interaction, modulated by the gut microbiota, influences essential physiological and cognitive functions, including mood regulation, stress response, and neuronal signaling. Dysbiosis, an imbalance in gut microbial composition, contributes to neurodegenerative disorders (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) by promoting inflammation and neuroinflammation, oxidative stress, neurotransmitter production and regulation, bloodbrain barrier integrity, protein aggregation, and misfolding. Microbial metabolites, such asshort-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives, play a crucial role in maintaining CNS homeostasis, whereas neurotoxic metabolites, like trimethylamine N-oxide (TMAO), exacerbate neurodegenerative pathology. Therapeutic interventions, including dietary modulation, prebiotics, probiotics, psychobiotics, fecal microbiota transplantation (FMT), vagus nerve stimulation (VNS), and small-molecule modulators, represent promising approaches to restore GBA balance and delay neurodegeneration. However, challenges remain in translating preclinical evidence into human application due to interindividual microbiome variability and limited mechanistic understanding. Emerging methodologies such as organ-on-a-chip models, wearable biosensors, and artificial intelligence-driven microbiome analytics hold potential for personalized, microbiota-based therapies. Standardization of biomarkers and study protocols will be essential to further clarify the GBA’s mechanistic involvement and therapeutic potential in neurodegenerative disease management.

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