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Mapping Gut Dysbiosis in Alzheimer’s using ML
Kumar PS.. Research Square, 2026-09-30
Topic: Genetics and APOE
Alzheimer’s disease is a progressive, currently irreversible, neurodegenerative disorder associated with the accumulation of β-Amyloid (Aβ) plaques between cells and tau (τ) tangles within cells. The gut-brain axis has been implicated in Alzheimer’s disease (AD) pathogenesis, yet experimental results regarding a gut microbial signature associated with AD remain inconsistent. In this study, I reprocessed a publicly uniformly reprocessed four publicly available fecal 16S rRNA cohorts (PRJNA554111, PRJNA489760, PRJNA633959, PRJNA734525; 413 samples, 218 AD / 195 controls) through a common amplicon-sequence-variant pipeline and evaluated cross-cohort generalizability using leave-one-dataset-out (LODO) validation across five machine-learning algorithm families. Cohort of origin was predictable from genus composition with 92.7% accuracy (chance 25%), whereas disease status reached only 0.74–0.81 AUC within studies and 0.57–0.64 AUC under LODO, a consistent generalization gap of approximately 0.17 AUC across all five models. Naive per-cohort standardization did not rescue LODO performance. Of 168 genera tested, 12 showed consistent direction across all four cohorts and survived FDR correction and showed depletion of butyrate-producing taxa in AD. The strongest signal was Lachnospira, detected in 46.8% of AD versus 75.9% of control samples (Fisher p = 1.2 × 10⁻⁹), consistent in direction across all four cohorts. SHAP feature attribution showed only Lachnospira and Akkermansia important in all four folds, corroborating the differential-abundance result. Together these results indicate that technical variation between studies exceeds disease-associated variation in AD microbiome data and that certain taxa, primarily butyrate producers whose prevalence was reduced, replicate across independent cohorts.
Key findings
- Alzheimer’s disease is a progressive, currently irreversible, neurodegenerative disorder associated with the accumulation of β-Amyloid (Aβ) plaques between cells and tau (τ) tangles within cells.
- The gut-brain axis has been implicated in Alzheimer’s disease (AD) pathogenesis, yet experimental results regarding a gut microbial signature associated with AD remain inconsistent.
- The strongest signal was Lachnospira, detected in 46.8% of AD versus 75.9% of control samples (Fisher p = 1.2 × 10⁻⁹), consistent in direction across all four cohorts.
- SHAP feature attribution showed only Lachnospira and Akkermansia important in all four folds, corroborating the differential-abundance result.
- Together these results indicate that technical variation between studies exceeds disease-associated variation in AD microbiome data and that certain taxa, primarily butyrate producers whose prevalence was reduced, replicate across independent cohorts.
Study details
- Effect size92.7%; 46.8%; 75.9%
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 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, 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 17 of the 62 points we could judge it on, which is 27 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 3 / 5 | Rated “moderate” 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 17 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 62 points we could judge it on is 27 out of 100. |
| Total | 27 / 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
Kumar, P. S. (2026). Mapping Gut Dysbiosis in Alzheimer’s using ML. Research Square. https://doi.org/10.21203/rs.3.rs-11197781/v1
Vancouver
Kumar PS. Mapping Gut Dysbiosis in Alzheimer’s using ML. Research Square. 2026. doi:10.21203/rs.3.rs-11197781/v1.
BibTeX
@article{kumar2026-76765211,
author = {Kumar, P. S.},
title = {{Mapping Gut Dysbiosis in Alzheimer’s using ML}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11197781/v1},
url = {https://doi.org/10.21203/rs.3.rs-11197781/v1}
}
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