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Gut Microbial Metabolism as a Dynamic Interface in Neurodegenerative Diseases
Kang Z, Meng R, Nie M, Wang T.. Metabolites, 2026-08-07
Topic: Gut, metabolism and diet
Gut microbial metabolites serve as functional mediators of gut–brain communication, linking microbial alterations to neurodegenerative pathology. How metabolite profiles shift during disease progression and interact with host genetic susceptibility remains poorly characterized. This review centers on Alzheimer’s disease (AD) as the primary model, with Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) included for cross-disease comparison. Across the AD continuum, microbial metabolic remodeling features reduced protective metabolites and elevated inflammation-related metabolites. Short-chain fatty acids (SCFAs), particularly butyrate, and indole-derived metabolites are altered from early cognitive impairment to clinical dementia. Trimethylamine N-oxide (TMAO), kynurenine intermediates and abnormal bile acid profiles accumulate and drive neuroinflammatory and metabolic disturbances. Mechanistically, metabolic shifts affect AD pathology through three interrelated pathways. Tryptophan-derived metabolites regulate immune homeostasis via aryl hydrocarbon receptor (AhR) signaling. SCFAs modulate epigenetic processes linked to Aβ and tau lesions. Intestinal and blood-brain barrier damage allows peripheral metabolic and inflammatory signals to reach the central nervous system. APOE4 alters lipid metabolism and systemic inflammation to modify individual metabolic susceptibility. Shared metabolic abnormalities including SCFA loss and barrier damage exist in PD and ALS, alongside disease-specific metabolic changes. Existing data support associations among host factors, the microbiome, and metabolite profiles, but longitudinal target-engagement studies remain limited.
Key findings
- SCFAs modulate epigenetic processes linked to Aβ and tau lesions.
- Intestinal and blood-brain barrier damage allows peripheral metabolic and inflammatory signals to reach the central nervous system.
- APOE4 alters lipid metabolism and systemic inflammation to modify individual metabolic susceptibility.
- Shared metabolic abnormalities including SCFA loss and barrier damage exist in PD and ALS, alongside disease-specific metabolic changes.
- Existing data support associations among host factors, the microbiome, and metabolite profiles, but longitudinal target-engagement studies remain limited.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 57/100
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 and multi-centre collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Metabolites) |
| 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 | 5 / 5 | 2026 — within 1 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 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
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APA 7th
Kang, Z., Meng, R., Nie, M., & Wang, T. (2026). Gut Microbial Metabolism as a Dynamic Interface in Neurodegenerative Diseases. Metabolites. https://doi.org/10.20944/preprints202608.0510.v1
Vancouver
Kang Z, Meng R, Nie M, Wang T. Gut Microbial Metabolism as a Dynamic Interface in Neurodegenerative Diseases. Metabolites. 2026. doi:10.20944/preprints202608.0510.v1.
BibTeX
@article{kang2026-99d180f0,
author = {Kang, Z. and Meng, R. and Nie, M. and Wang, T.},
title = {{Gut Microbial Metabolism as a Dynamic Interface in Neurodegenerative Diseases}},
journal = {Metabolites},
year = {2026},
doi = {10.20944/preprints202608.0510.v1},
url = {https://doi.org/10.20944/preprints202608.0510.v1}
}
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