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Published on: May 20, 2024
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Fecal Short-Chain Fatty Acids Vary by Sex and Amyloid Status
Jessamine F Kuehn1,2, Qijun Zhang1, Margo B Heston3
1Department of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Medrxiv : the Preprint Server for Health Sciences
|August 6, 2025
Summary
Gut microbes produce short-chain fatty acids (SCFAs) linked to Alzheimer's disease (AD). Higher SCFA levels and specific bacteria correlate with reduced amyloid and slower cognitive decline in humans.
Area of Science:
- Microbiome research
- Neuroscience
- Human health
Background:
- Gut microbes produce short-chain fatty acids (SCFAs) that impact Alzheimer's disease (AD) pathology in animal models.
- The role of SCFAs in human AD progression remains less understood.
Purpose of the Study:
- To investigate the association between gut microbiome, SCFAs, and AD pathology in humans.
- To explore the relationship between gut microbial metabolites and cognitive function across the AD continuum.
Main Methods:
- Fecal samples from 287 participants were analyzed for SCFA levels and bacterial abundances.
- Regression analyses were used to examine associations between SCFAs, microbes, AD pathology, and cognition.
Main Results:
- Fecal propionate and isovalerate, along with propionate-producing bacteria, showed inverse associations with amyloid status.
- Propionate was identified as a mediator in sex-specific associations between SCFAs and cerebrospinal fluid (CSF) biomarkers.
- Elevated SCFA levels were linked to a slower rate of cognitive decline.
Conclusions:
- This study establishes a link between SCFAs, propionate-producing bacteria, and AD in humans.
- Findings suggest potential therapeutic strategies involving diet and probiotics to modulate SCFA production for ameliorating AD progression.
