Gut microbiome alterations in Alzheimer’s disease
Open accessAbstract
Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
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These changes include reductions in beneficial genera such as Lactobacillus and Bifidobacterium, alongside increases in pro-inflammatory taxa like Enterobacteriaceae.
“These include reductions in beneficial genera such as Lactobacillus and Bifidobacterium, alongside increases in pro-inflammatory taxa like Enterobacteriaceae64.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [64]
The Results section, “AD is Associated with Changes in the Gut Microbiome” (page unavailable), reports decreased Bifidobacterium in participants with Alzheimer’s disease compared with controls. It reports increased Bacteroides and Bilophila, but does not report decreased Lactobacillus or increased Enterobacteriaceae; searches for those taxa found no supporting passage in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredStudies using 16S rRNA gene sequencing and shotgun metagenomic sequencing have consistently identified significant changes in the gut microbiota composition of individuals with AD.
“Studies using 16S rRNA gene sequencing and shotgun metagenomic sequencing have consistently identified significant changes in the gut microbiota composition of individuals with AD.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [64]
The Discussion and Results report that 16S rRNA gene sequencing found significant differences in gut microbiome composition between participants with and without AD. The Methods describe predictive metagenomics based on 16S data, not shotgun metagenomic sequencing. This paper therefore does not support attributing findings from both sequencing approaches—or a consistent pattern across multiple studies—to it. (LLM, conf=0.91)
Experimental — accuracy not yet measuredHuman studies link gut microbiota to neurodegenerative diseases.
“Human studies show associations between gut microbiota and neurodegenerative diseases148.”
From Microglia in neurodegeneration (2018) · cites this paper as [148]
A variety of genetic and environmental factors have been implicated in AD etiopathogenesis, including contributions from gut microbiota.
“A variety of genetic and environmental factors have been implicated in AD etiopathogenesis, including contributions from gut microbiota [13–15].”
From The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease (2018) · cites this paper as [15]
Human studies comparing the composition of the GM of elderly participants suffering from cognitive impairment with healthy individuals indicate significant changes in GM composition, specifically an increase in pro-inflammatory taxa and a reduction in anti-inflammatory taxa.
“Human studies comparing the composition of the GM of elderly participants suffering from cognitive impairment with healthy individuals indicate significant changes in GM composition. Specifically, there is an increase in pro-inflammatory taxa and a reduction in anti-inflammatory taxa (104–109).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [105]
Within the Firmicutes, the families Ruminococcaceae, Turicibacteraceae, and Clostridiaceae were all less abundant in Alzheimer's disease patients.
“Within the Firmicutes, the families Ruminococcaceae, Turicibacteraceae, and Clostridiaceae were all less abundant in AD patient (160).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [160]
Diseases of cognitive decline, such as Alzheimer's disease and vascular dementia, are associated with aberrant microbial compositions when compared with healthy controls.
“Diseases of cognitive decline, such as Alzheimer's disease and vascular dementia, are associated with aberrant microbial compositions when compared with healthy controls (297).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [297]
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- Authors
- Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., Bendlin, B. B., & Rey, F. E.
- Affiliations
- University of Wisconsin–Madison (US)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Bendlin, Barbara B.
- Rey, Federico E.
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-10-19
- Volume
- 7
- Issue
- 1
- Pages
- 13537-13537
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5648830
- OpenAlex
- W2761210275
- Cited by
- 2,137
- References
- 70
- Citations by year
- 2026: 205 · 2025: 322 · 2024: 328 · 2023: 269 · 2022: 339 · 2021: 283 · 2020: 205 · 2019: 119 · 2018: 64 · 2017: 1
- FWCI
- 43.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Alzheimer's Association (R01 AG027161, R01 AG037639, R01 AG021155)
- Torsten Söderbergs Stiftelse
- Rush University
- Georgia Clinical and Translational Science Alliance (UL1TR000427)
- Royal Swedish Academy of Sciences
- Vetenskapsrådet
- National Institutes of Health (UL1TR000427, NIH P50, AG027161, AG037639, NIH P50 AG033514, AG033514)
- Institute for Clinical and Translational Research, University of Wisconsin, Madison (UL1TR000427)
- National Institute on Aging (RF1AG027161, R01AG037639, P50AG033514, R01AG021155, R01AG027161, R56AG037639)
- National Institute of General Medical Sciences (T32GM008692)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, gut microbiota, dementia, fecal microbiota, microbial diversity, Firmicutes, Bacteroidetes, Bifidobacterium, cerebrospinal fluid biomarkers, amyloid deposition, gut-brain axis, therapeutic target
- MeSH terms
- Bacillota, Gastrointestinal Microbiome, Aged, Alzheimer Disease, Bifidobacterium, Feces, Female, Humans, Male, Biomarkers, Case-Control Studies, tau Proteins, Bacteroidetes
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