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Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets
Ce Chen, Guo-Qing Wang, Dai-di Li, Feng Zhang. Molecular biomedicine, 2025-09-15
Topic: Gut, metabolism and diet
The microbiota-gut-brain axis (MGBA) is an intricate bidirectional communication network that links intestinal microbiota with the central nervous system (CNS) through immune, neural, endocrine, and metabolic pathways. Emerging evidence suggests that dysregulation of the MGBA plays pivotal roles in the onset and progression of neurodegenerative diseases. This review outlines the key molecular mechanisms by which gut microbes modulate neuroinflammation, blood-brain barrier integrity, protein misfolding, and neuronal homeostasis. We discuss how microbial metabolites, such as short-chain fatty acids, tryptophan derivatives, and bile acids, interact with host to influence CNS functions. Disease-specific features are described across Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis, emphasizing the distinct and overlapping pathways through which gut dysbiosis may contribute to pathogenesis. We further explore the translational potential of microbiota-targeted therapies, including probiotics, fecal microbiota transplantation, dietary interventions, and small-molecule modulators. While preclinical results are promising, clinical trials reveal considerable variability, highlighting the need for personalized approaches and robust biomarkers. Challenges remain in deciphering causal relationships, accounting for inter-individual variability, and ensuring reproducibility in therapeutic outcomes. Future research should integrate multi-omics strategies, longitudinal human cohorts, and mechanistic models to clarify the role of the MGBA in neurodegeneration. Collectively, understanding the MGBA provides a transformative perspective on neurodegenerative disease mechanisms and offers innovative therapeutic avenues that bridge neurology, microbiology, and precision medicine.
Key findings
- Emerging evidence suggests that dysregulation of the MGBA plays pivotal roles in the onset and progression of neurodegenerative diseases.
- While preclinical results are promising, clinical trials reveal considerable variability, highlighting the need for personalized approaches and robust biomarkers.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 59/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 33 of the 56 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular biomedicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40952592) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 33 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 33 of the 56 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Chen, C., Wang, G.-Q., Li, D.-d., & Zhang, F. (2025). Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets. Molecular biomedicine. https://doi.org/10.1186/s43556-025-00307-1
Vancouver
Chen C, Wang G.-Q, Li D.-d, Zhang F. Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets. Molecular biomedicine. 2025. doi:10.1186/s43556-025-00307-1. PMID: 40952592.
BibTeX
@article{chen2025-40952592,
author = {Chen, Ce and Wang, Guo-Qing and Li, Dai-di and Zhang, Feng},
title = {{Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets}},
journal = {Molecular biomedicine},
year = {2025},
doi = {10.1186/s43556-025-00307-1},
pmid = {40952592},
url = {https://doi.org/10.1186/s43556-025-00307-1}
}
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