Associations of gut bacterial classes Clostridia and Deltaproteobacteria with type 2 diabetes and Alzheimer’s disease: A two-sample Mendelian randomization study
Xueying Gao, Lingling Wang. Medicine, 2026-05-15
Topic: Amyloid, tau and blood-test diagnosis
Using a 2-sample Mendelian randomization (MR) approach, we evaluated MR evidence for genetically proxied effects of 10 pre-specified gut bacterial classes on type 2 diabetes mellitus (T2DM) and Alzheimer disease (AD), and assessed MR evidence for a direct genetically proxied effect of T2DM on AD. Mediation by T2DM was explored where feasible. We performed 2-sample MR using MiBioGen gut microbiota GWAS summary statistics as exposure, and DIAMANTE (T2DM) and European AD GWAS data as outcomes. Inverse-variance weighted (IVW) MR was the primary analysis, with MR-Egger, weighted median, and weighted mode as sensitivity analyses. Heterogeneity and directional pleiotropy were assessed, and IVW results were false discovery rate (FDR) corrected using Benjamini-Hochberg. MR analysis using 184 independent SNPs provided no robust evidence for a direct genetically proxied effect of T2DM on AD risk (IVW odds ratio [OR] = 0.98, 95% confidence interval [CI]: 0.94-1.02, P = .28). After FDR correction, higher genetically predicted Clostridia abundance was associated with lower AD risk (IVW OR = 0.86, 95% CI: 0.77-0.96, FDR < 0.05), and higher genetically predicted Deltaproteobacteria abundance was associated with higher T2DM risk (IVW OR = 1.11, 95% CI: 1.04-1.20, FDR < 0.05). Other classes were not significant after FDR correction. Reverse MR and multivariable MR were not testable due to insufficient SNP overlap after harmonization (effective SNPs < 3). These findings provide MR evidence consistent with genetically proxied effects of Clostridia on AD and Deltaproteobacteria on T2DM and do not support robust MR evidence for a direct genetically proxied effect of T2DM on AD. Results are hypothesis-generating and require replication in diverse ancestries and follow-up mechanistic/experimental studies, given that included GWAS sources are predominantly of European ancestry.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Gao, X., & Wang, L. (2026). Associations of gut bacterial classes Clostridia and Deltaproteobacteria with type 2 diabetes and Alzheimer’s disease: A two-sample Mendelian randomization study. Medicine. https://doi.org/10.1097/md.0000000000048685
Vancouver
Gao X, Wang L. Associations of gut bacterial classes Clostridia and Deltaproteobacteria with type 2 diabetes and Alzheimer’s disease: A two-sample Mendelian randomization study. Medicine. 2026. doi:10.1097/md.0000000000048685. PMID: 42152315.
BibTeX
@article{gao2026-42152315,
author = {Gao, Xueying and Wang, Lingling},
title = {{Associations of gut bacterial classes Clostridia and Deltaproteobacteria with type 2 diabetes and Alzheimer’s disease: A two-sample Mendelian randomization study}},
journal = {Medicine},
year = {2026},
doi = {10.1097/md.0000000000048685},
pmid = {42152315},
url = {https://doi.org/10.1097/md.0000000000048685}
}
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Key findings
- Heterogeneity and directional pleiotropy were assessed, and IVW results were false discovery rate (FDR) corrected using Benjamini-Hochberg.
- After FDR correction, higher genetically predicted Clostridia abundance was associated with lower AD risk (IVW OR = 0.86, 95% CI: 0.77-0.96, FDR < 0.05), and higher genetically predicted Deltaproteobacteria abundance was associated with higher T2DM risk (IVW OR = 1.11, 95% CI: 1.04-1.20, FDR < 0.05).
- Other classes were not significant after FDR correction.
- These findings provide MR evidence consistent with genetically proxied effects of Clostridia on AD and Deltaproteobacteria on T2DM and do not support robust MR evidence for a direct genetically proxied effect of T2DM on AD.
- Results are hypothesis-generating and require replication in diverse ancestries and follow-up mechanistic/experimental studies, given that included GWAS sources are predominantly of European ancestry.
Why it matters
This genetic analysis found no robust evidence that type 2 diabetes directly affects Alzheimer's disease risk, but it did find that higher genetically predicted Clostridia abundance was associated with lower Alzheimer's disease risk. These findings come from statistical genetic methods and do not establish that changing gut bacteria would prevent or treat Alzheimer's disease.
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Study details
- Effect sizeOR = 0.86; OR = 1.11
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Medicine) |
| Journal's citation record | 3 / 4 | Medicine: journal h-index 285 (OpenAlex, 2026-10-29) |
| 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 | 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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 2 / 6 | Cited 1.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Lingling Wang: h-index 59 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Beihua University: institution h-index 123 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42152315) |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 100 | — |
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