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The Gut-Brain Axis in Alzheimer’s Disease: Microbiota as a Key Contributor to Disease Pathogenesis
Tasnády KR, Ananthasabesan J, Visser PJ, Melotte V, Delvenne A.. Preprints.org, 2026-08-31
Topic: Gut, metabolism and diet
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder influenced by genetic, environmental, and lifestyle factors. Increasing evidence indicates that the gut microbiota composition is a key modulator of AD pathogenesis, driving neuroinflammation, and amyloid and tau pathology through the microbiota–gut–brain axis. This review synthesizes current findings on the mechanistic pathways by which alterations in gut microbiota composition contribute to AD, focusing on immune, metabolic, and neuronal routes of gut–brain communication. We describe how alterations in gut microbial composition impair intestinal barrier integrity, enabling the translocation of microbial components, such as lipopolysaccharides, bacterial amyloids, trimethylamine-N-oxide, secondary bile acids, and short-chain fatty acids, into the circulation. These circulating factors disrupt blood–brain and blood–cerebrospinal fluid barriers, amplify systemic and central inflammation, and promote amyloid and tau pathology. We further compare microbial signatures in AD with those observed in related comorbidities, including obesity, type 2 diabetes mellitus, rheumatoid arthritis, inflammatory bowel disease, and irritable bowel syndrome. Overlapping patterns of reduced beneficial taxa alongside increases in pro-inflammatory taxa suggest shared microbiota-mediated mechanisms underlying increased AD risk in these conditions. Finally, we discuss emerging microbiota-targeted interventions, including probiotics, fecal microbiota transplantation, anti-inflammatory therapies and metabolic interventions, that may restore microbial homeostasis and modulate neuropathological processes. Collectively, this review underscores the bidirectional interplay between the gut microbiota and the brain in AD pathogenesis and highlights the therapeutic potential of microbiota-based strategies for early intervention, disease modification, and improved clinical outcomes.
Key findings
- Increasing evidence indicates that the gut microbiota composition is a key modulator of AD pathogenesis, driving neuroinflammation, and amyloid and tau pathology through the microbiota–gut–brain axis.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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
Tasnády, K. R., Ananthasabesan, J., Visser, P. J., Melotte, V., & Delvenne, A. (2026). The Gut-Brain Axis in Alzheimer’s Disease: Microbiota as a Key Contributor to Disease Pathogenesis. Preprints.org. https://doi.org/10.20944/preprints202608.2280.v1
Vancouver
Tasnády KR, Ananthasabesan J, Visser PJ, Melotte V, Delvenne A. The Gut-Brain Axis in Alzheimer’s Disease: Microbiota as a Key Contributor to Disease Pathogenesis. Preprints.org. 2026. doi:10.20944/preprints202608.2280.v1.
BibTeX
@article{tasnady2026-918169a2,
author = {Tasnády, K. R. and Ananthasabesan, J. and Visser, P. J. and Melotte, V. and Delvenne, A.},
title = {{The Gut-Brain Axis in Alzheimer’s Disease: Microbiota as a Key Contributor to Disease Pathogenesis}},
journal = {Preprints.org},
year = {2026},
doi = {10.20944/preprints202608.2280.v1},
url = {https://doi.org/10.20944/preprints202608.2280.v1}
}
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