The microbiota-gut-brain axis emerged as a therapeutic target across neurodegenerative and neuropsychiatric conditions, with 2025 studies demonstrating that fecal microbiota transplantation, probiotics, and dietary interventions can modulate neuroinflammation, cognitive function, and mood disorders [1][2][3][4][5].
FMT in neurodegenerative disorders showed promise for Parkinson's disease, Alzheimer's disease, multiple sclerosis, and ALS through mechanisms including reduction of neuroinflammation, strengthening gut barrier integrity, regulating neurotransmitter production, and reinstating microbial diversity [1]. Advanced FMT techniques for gut dysbiosis-related diseases demonstrated high efficacy in recurrent Clostridioides difficile infection while showing variable results for inflammatory bowel disease, irritable bowel syndrome, and metabolic disorders, with future research needed to optimize donor selection, recipient characteristics, and treatment protocols [2].
Animal studies in 5XFAD Alzheimer's model mice demonstrated that FMT from healthy donors improved cognitive function, reduced neuroinflammation and oxidative stress, and modulated acetylcholine levels, providing novel insights into gut-brain axis dynamics [3]. Comprehensive reviews highlighted gut dysbiosis contributions to anxiety, depression, bipolar disorder, PTSD, and neurodegenerative diseases through alterations in short-chain fatty acids, bile acids, tryptophan metabolites, and immune signaling pathways [4][5].
Why it matters:
For clinicians: Microbiome-based interventions offer novel therapeutic approaches for conditions with limited treatment options. FMT shows established efficacy for recurrent C. difficile infection (>90% cure rates) and emerging evidence for neuropsychiatric applications. Dietary modifications (Mediterranean diet, fiber supplementation), probiotics, and prebiotics provide lower-risk interventions that may complement standard therapies. However, FMT safety concerns include pathogen transmission, immune responses, and variable efficacy across indications. Patient selection, donor screening protocols, and appropriate clinical contexts require careful consideration.
For researchers: The gut-brain axis represents a paradigm shift in understanding systemic disease. Future directions include defining optimal microbial consortia for specific conditions, elucidating mechanisms linking specific bacterial metabolites to brain function, developing synthetic microbial communities to replace donor-dependent FMT, integrating AI-driven microbiome analysis for personalized interventions, and conducting rigorous RCTs to establish clinical utility across diverse patient populations. Outstanding questions include durability of effects, optimal timing and frequency of interventions, and biomarkers predicting treatment response.
References
- Eslami M, Adampour Z, Fadaee Dowlat B, et al. A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders. Biomedicines. 2025;13(4):915. doi: 10.3390/biomedicines13040915
PubMed: https://pubmed.ncbi.nlm.nih.gov/40299512/ - Hou S, Yu J, Li Y, et al. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. Adv Sci (Weinh). 2025;12(13):e2413197. doi: 10.1002/advs.202413197
PubMed: https://pubmed.ncbi.nlm.nih.gov/40013938/ - Upadhyay P, Kumar S, Tyagi A, et al. Gut Microbiome rewiring via fecal transplants: Uncovering therapeutic avenues in Alzheimer's disease models. BMC Neurosci. 2025;26(1):39. doi: 10.1186/s12868-025-00953-9
PubMed: https://pubmed.ncbi.nlm.nih.gov/40615821/ - Jafari S, Dehghan P, Sabahi A, et al. The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention. Front Cell Infect Microbiol. 2025. [Epub ahead of print]
PubMed: https://pubmed.ncbi.nlm.nih.gov/41104042/ - Shabani M, Ghoshehy A, Mottaghi AM, et al. The relationship between gut microbiome and human diseases: mechanisms, predisposing factors and potential intervention. Front Cell Infect Microbiol. 2025;15:1516010. doi: 10.3389/fcimb.2025.1516010
PubMed: https://pubmed.ncbi.nlm.nih.gov/40395507/