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Gut Microbiota Composition Is Related to AD Pathology
Verhaar BJH, Hendriksen HMA, de Leeuw FA, Doorduijn AS, van Leeuwenstijn M, Teunissen CE, Barkhof F, Scheltens P et al.. Frontiers in immunology, 2022-01-31
Topic: Brain proteins, microglia and lab models
Introduction Several studies have reported alterations in gut microbiota composition of Alzheimer's disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Materials and methods We included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE. Results The machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis , and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status. Conclusions Gut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.
Key findings
- Results The machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63.
- Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis , and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity.
- We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status.
- Conclusions Gut microbiota composition was associated with amyloid and p-tau status.
- We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.
Why it matters
This study investigated associations between gut microbiota composition and Alzheimer's disease biomarkers using machine learning in patients with dementia, mild cognitive impairment and subjective cognitive decline. It found modest prediction and some microbial associations, but it is about correlations with biomarkers, not treatment or cure.
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Study details
- Participants170
- Evidence strengthModerate
How this study scored 61/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in immunology) |
| Journal's citation record | 3 / 4 | Frontiers in Immunology: journal h-index 352 (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 | 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 170 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 225 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 32.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 13.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 3 / 4 | Cited 154 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Wiesje M. van der Flier: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35173707) |
| Free to read | 2 / 2 | Free to read |
| Total | 61 / 100 | — |
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Read the original
- DOI: 10.3389/fimmu.2021.794519
- PubMed: 35173707
- Original source →
- Free full text: Frontiers in Immunology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Verhaar, B. J. H., Hendriksen, H. M. A., de Leeuw, F. A., Doorduijn, A. S., van Leeuwenstijn, M., Teunissen, C. E., et al. (2021). Gut Microbiota Composition Is Related to AD Pathology. Frontiers in immunology. https://doi.org/10.3389/fimmu.2021.794519
Vancouver
Verhaar BJH, Hendriksen HMA, de Leeuw FA, Doorduijn AS, van Leeuwenstijn M, Teunissen CE, et al. Gut Microbiota Composition Is Related to AD Pathology. Frontiers in immunology. 2021. doi:10.3389/fimmu.2021.794519. PMID: 35173707.
BibTeX
@article{verhaar2021-35173707,
author = {Verhaar, B. J. H. and Hendriksen, H. M. A. and de Leeuw, F. A. and Doorduijn, A. S. and van Leeuwenstijn, M. and Teunissen, C. E. and Barkhof, F. and Scheltens, P. and others},
title = {{Gut Microbiota Composition Is Related to AD Pathology}},
journal = {Frontiers in immunology},
year = {2021},
doi = {10.3389/fimmu.2021.794519},
pmid = {35173707},
url = {https://doi.org/10.3389/fimmu.2021.794519}
}
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