Aging Gut-Brain Interactions: Pro-Inflammatory Gut Bacteria Are Elevated in Fecal Samples from Individuals Living with Alzheimer’s Dementia

Alison I. C. Donaldson; Claire L. Fyfe; Jennifer C. Martin; Ellen E. Smith; Graham W. Horgan; Phyo K. Myint; Alexandra M. Johnstone; Karen P. Scott

doi:10.3390/geriatrics10020037

Aging Gut-Brain Interactions: Pro-Inflammatory Gut Bacteria Are Elevated in Fecal Samples from Individuals Living with Alzheimer’s Dementia

Alison I. C. Donaldson^* (Corresponding Author), Claire L. Fyfe, Jennifer C. Martin, Ellen E. Smith, Graham W. Horgan, Phyo K. Myint, Alexandra M. Johnstone, Karen P. Scott

^*Corresponding author for this work

Biomathematics and Statistics Scotland

Research output: Contribution to journal › Article › peer-review

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Abstract

Background/Objectives: Alzheimer’s disease (AD) is the most common form of dementia, characterized by an irreversible decline in cognitive function. The pathogenesis of several neurodegenerative disorders has been linked to changes in the gut microbiota, transmitted through the gut-brain axis. Methods: We set out to establish by case-control study methodology whether there were any differences in the composition and/or function of the gut microbiota between older resident adults in care homes with or without an AD diagnosis via analysis of the microbial composition from fecal samples. Results: The microbial composition, determined by 16S rRNA gene profiling, indicated that AD sufferers had significantly increased proportions of Escherichia/Shigella and Clostridium_sensu_stricto_1, and significantly decreased proportions of Bacteroides, Faecalibacterium, Blautia, and Roseburia species. The increase in potentially pro-inflammatory bacteria was consistent with slightly higher concentrations of calprotectin, a biomarker of gut inflammation. Fecal concentrations of most microbial metabolites measured were similar across groups, although participants with AD had significantly increased proportions of the branched-chain fatty acid, iso-butyrate, and lower overall concentrations of total short chain fatty acids. Conclusions: Participants with Alzheimer’s disease have several key differences within their gut microbiota profile, in contrast to care home residents without Alzheimer’s disease. The altered microbiome included both compositional and functional changes linked to poorer health and gut inflammation.

Original language	English
Article number	37
Number of pages	18
Journal	Geriatrics
Volume	10
Issue number	2
Early online date	7 Mar 2025
DOIs	https://doi.org/10.3390/geriatrics10020037
Publication status	Published - Apr 2025

Bibliographical note

We would like to thank the care homes, participants, and relatives without whom this study would not have been possible. We are also indebted to the help of the research nurse team [Sandra Mann, Eunice Morgan and Bolanle Brikkins]. We also greatly appreciate the assistance of the Rowett Analytical Department with SCFA analysis, and the input of students Karen Houston and Robert F. Graham, and medical student Ross Lilley during the study.

Data Availability Statement

Data availability: The datasets generated for this study can be found in the European Nucleotide Archive, accession number PRJEB64619. These data are private until acceptance of the manuscript.

Supplementary Information: Supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/geriatrics10020037/s1

Keywords

brain
Alzheimer’s disease
gut-brain axis
fecal microbiota

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Cite this

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title = "Aging Gut-Brain Interactions: Pro-Inflammatory Gut Bacteria Are Elevated in Fecal Samples from Individuals Living with Alzheimer{\textquoteright}s Dementia",

abstract = "Background/Objectives: Alzheimer{\textquoteright}s disease (AD) is the most common form of dementia, characterized by an irreversible decline in cognitive function. The pathogenesis of several neurodegenerative disorders has been linked to changes in the gut microbiota, transmitted through the gut-brain axis. Methods: We set out to establish by case-control study methodology whether there were any differences in the composition and/or function of the gut microbiota between older resident adults in care homes with or without an AD diagnosis via analysis of the microbial composition from fecal samples. Results: The microbial composition, determined by 16S rRNA gene profiling, indicated that AD sufferers had significantly increased proportions of Escherichia/Shigella and Clostridium_sensu_stricto_1, and significantly decreased proportions of Bacteroides, Faecalibacterium, Blautia, and Roseburia species. The increase in potentially pro-inflammatory bacteria was consistent with slightly higher concentrations of calprotectin, a biomarker of gut inflammation. Fecal concentrations of most microbial metabolites measured were similar across groups, although participants with AD had significantly increased proportions of the branched-chain fatty acid, iso-butyrate, and lower overall concentrations of total short chain fatty acids. Conclusions: Participants with Alzheimer{\textquoteright}s disease have several key differences within their gut microbiota profile, in contrast to care home residents without Alzheimer{\textquoteright}s disease. The altered microbiome included both compositional and functional changes linked to poorer health and gut inflammation.",

keywords = "brain, Alzheimer{\textquoteright}s disease, gut-brain axis, fecal microbiota",

author = "Donaldson, {Alison I. C.} and Fyfe, {Claire L.} and Martin, {Jennifer C.} and Smith, {Ellen E.} and Horgan, {Graham W.} and Myint, {Phyo K.} and Johnstone, {Alexandra M.} and Scott, {Karen P.}",

note = "We would like to thank the care homes, participants, and relatives without whom this study would not have been possible. We are also indebted to the help of the research nurse team [Sandra Mann, Eunice Morgan and Bolanle Brikkins]. We also greatly appreciate the assistance of the Rowett Analytical Department with SCFA analysis, and the input of students Karen Houston and Robert F. Graham, and medical student Ross Lilley during the study.",

year = "2025",

month = apr,

doi = "10.3390/geriatrics10020037",

language = "English",

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T2 - Pro-Inflammatory Gut Bacteria Are Elevated in Fecal Samples from Individuals Living with Alzheimer’s Dementia

AU - Donaldson, Alison I. C.

AU - Fyfe, Claire L.

AU - Martin, Jennifer C.

AU - Smith, Ellen E.

AU - Horgan, Graham W.

AU - Myint, Phyo K.

AU - Johnstone, Alexandra M.

AU - Scott, Karen P.

N1 - We would like to thank the care homes, participants, and relatives without whom this study would not have been possible. We are also indebted to the help of the research nurse team [Sandra Mann, Eunice Morgan and Bolanle Brikkins]. We also greatly appreciate the assistance of the Rowett Analytical Department with SCFA analysis, and the input of students Karen Houston and Robert F. Graham, and medical student Ross Lilley during the study.

PY - 2025/4

Y1 - 2025/4

N2 - Background/Objectives: Alzheimer’s disease (AD) is the most common form of dementia, characterized by an irreversible decline in cognitive function. The pathogenesis of several neurodegenerative disorders has been linked to changes in the gut microbiota, transmitted through the gut-brain axis. Methods: We set out to establish by case-control study methodology whether there were any differences in the composition and/or function of the gut microbiota between older resident adults in care homes with or without an AD diagnosis via analysis of the microbial composition from fecal samples. Results: The microbial composition, determined by 16S rRNA gene profiling, indicated that AD sufferers had significantly increased proportions of Escherichia/Shigella and Clostridium_sensu_stricto_1, and significantly decreased proportions of Bacteroides, Faecalibacterium, Blautia, and Roseburia species. The increase in potentially pro-inflammatory bacteria was consistent with slightly higher concentrations of calprotectin, a biomarker of gut inflammation. Fecal concentrations of most microbial metabolites measured were similar across groups, although participants with AD had significantly increased proportions of the branched-chain fatty acid, iso-butyrate, and lower overall concentrations of total short chain fatty acids. Conclusions: Participants with Alzheimer’s disease have several key differences within their gut microbiota profile, in contrast to care home residents without Alzheimer’s disease. The altered microbiome included both compositional and functional changes linked to poorer health and gut inflammation.

AB - Background/Objectives: Alzheimer’s disease (AD) is the most common form of dementia, characterized by an irreversible decline in cognitive function. The pathogenesis of several neurodegenerative disorders has been linked to changes in the gut microbiota, transmitted through the gut-brain axis. Methods: We set out to establish by case-control study methodology whether there were any differences in the composition and/or function of the gut microbiota between older resident adults in care homes with or without an AD diagnosis via analysis of the microbial composition from fecal samples. Results: The microbial composition, determined by 16S rRNA gene profiling, indicated that AD sufferers had significantly increased proportions of Escherichia/Shigella and Clostridium_sensu_stricto_1, and significantly decreased proportions of Bacteroides, Faecalibacterium, Blautia, and Roseburia species. The increase in potentially pro-inflammatory bacteria was consistent with slightly higher concentrations of calprotectin, a biomarker of gut inflammation. Fecal concentrations of most microbial metabolites measured were similar across groups, although participants with AD had significantly increased proportions of the branched-chain fatty acid, iso-butyrate, and lower overall concentrations of total short chain fatty acids. Conclusions: Participants with Alzheimer’s disease have several key differences within their gut microbiota profile, in contrast to care home residents without Alzheimer’s disease. The altered microbiome included both compositional and functional changes linked to poorer health and gut inflammation.

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KW - Alzheimer’s disease

KW - gut-brain axis

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DO - 10.3390/geriatrics10020037

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IS - 2

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ER -

Aging Gut-Brain Interactions: Pro-Inflammatory Gut Bacteria Are Elevated in Fecal Samples from Individuals Living with Alzheimer’s Dementia

Abstract

Bibliographical note

Data Availability Statement

Keywords

Access to Document

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