Change in gut microbiome precedes symptomatic Alzheimer's disease and is correlated with amyloid-beta accumulation in the brain
- 1South Australian Health and Medical Research Institute
Abstract
INTRODUCTIONAlzheimers disease (AD) begins with cerebral amyloid-beta (AP) deposition decades before clinical symptoms. While the microbiota-gut-brain axis has been implicated in AD, its role in this preclinical phase remains unclear. We examined potential links between gut microbiome features and presymptomatic cerebral Ap burden.
METHODSAsymptomatic individuals (n=101, median age 70.0 years, 53% female) underwent cognitive assessment, cerebral Ap quantification, and stool metagenomic sequencing. Associations between microbial characteristics and Ap levels were performed using multivariable-adjusted ordinal logistic regression.
RESULTSGut microbiota composition varied with Ap levels (p(perm)=0.03, R2=0.014). Higher Ap was associated with increased Alistipes communis, and decreased Anaerotignum faecicola and Eubacterium rectale, abundance (q<0.001). Ap-associated microbiome traits corresponded to lower biosynthetic capacity for y-aminobutyric acid, and systemic regulators of immunity and autophagy (q<0.01).
DISCUSSIONEarly Ap accumulation is associated with distinct gut microbial signatures and reduced neuroactive metabolic potential, identifying targets for potential preclinical AD intervention.
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BibTeX
@misc{shoubridge2026change,
title = {{Change in gut microbiome precedes symptomatic Alzheimer's disease and is correlated with amyloid-beta accumulation in the brain}},
author = {A. P. Shoubridge and S. K. Manning and S. Tan and S. Kidson and A. Richard and J. Trinder and S. Miller and K. Laver and M. Rahja and J. Robertson and M. Crotty and S. L. Taylor and G. B. Rogers},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.26365677},
url = {https://www.medrxiv.org/content/10.64898/2026.10.15.26365677v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Change in gut microbiome precedes symptomatic Alzheimer's disease and is correlated with amyloid-beta accumulation in the brain
AU - A. P. Shoubridge
AU - S. K. Manning
AU - S. Tan
AU - S. Kidson
AU - A. Richard
AU - J. Trinder
AU - S. Miller
AU - K. Laver
AU - M. Rahja
AU - J. Robertson
AU - M. Crotty
AU - S. L. Taylor
AU - G. B. Rogers
PY - 2026
DA - 2026/10/15
PB - medRxiv
DO - 10.64898/2026.10.15.26365677
UR - https://www.medrxiv.org/content/10.64898/2026.10.15.26365677v1
AB - INTRODUCTIONAlzheimers disease (AD) begins with cerebral amyloid-beta (AP) deposition decades before clinical symptoms. While the microbiota-gut-brain axis has been implicated in AD, its role in this preclinical phase remains unclear. We examined potential links between gut microbiome features and presymptomatic cerebral Ap burden. METHODSAsymptomatic individuals (n=101, median age 70.0 years, 53% female) underwent cognitive assessment, cerebral Ap quantification, and stool metagenomic sequencing. Associations between microbial characteristics and Ap levels were performed using multivariable-adjusted ordinal logistic regression. RESULTSGut microbiota composition varied with Ap levels (p(perm)=0.03, R2=0.014). Higher Ap was associated with increased Alistipes communis, and decreased Anaerotignum faecicola and Eubacterium rectale, abundance (q<0.001). Ap-associated microbiome traits corresponded to lower biosynthetic capacity for y-aminobutyric acid, and systemic regulators of immunity and autophagy (q<0.01). DISCUSSIONEarly Ap accumulation is associated with distinct gut microbial signatures and reduced neuroactive metabolic potential, identifying targets for potential preclinical AD intervention.
ER -