Abstract
Background
Short-chain fatty acids are believed to mediate microbiome-host interactions. Acetic acid is the most abundant systemic short-chain fatty acid, but knowledge about its physiological functions comes mainly from rodent experiments, with limited human research particularly in the aging population.
Methods
In this cross-sectional observational study, we examined the association between the gut microbiota and plasma acetic acid, specifically investigating the mediating effect of plasma acetic acid on the relationship between the gut microbiota and blood lipid profile, body composition, brain gray matter volume, and cognitive performance in older adults. The gut microbiome was profiled using full-length 16S rRNA gene sequencing to enable taxonomic classification.
Results
Here we show that specific gut microbial co-abundance group is associated with plasma acetic acid levels. Higher plasma levels of acetic acid are associated with lower plasma triglyceride levels, higher high-density lipoprotein cholesterol levels, lower body mass index, lower body fat mass, higher thalamic volume, and higher cognitive performance in certain domains. Additionally, we show that plasma acetic acid mediates the relationship between gut microbiome on these health measures.
Conclusions
This study identifies gut microbial group linked to plasma acetic acid and demonstrates its potential mediating role between the gut microbiome, blood lipid profile, brain volume and cognitive function in older adults. These insights pave the way for future research and highlight the potential of acetic acid as an intervention target for metabolic and neurological diseases, contributing to strategies that promote healthy aging.
Plain language summary
The gut microbiome plays an important role in maintaining human health, partly through producing short-chain fatty acids such as acetic acid. However, little is known about how acetic acid relates to metabolic and brain health in older adults. In this study, we examined stool and blood samples from older individuals to assess the relationship between gut bacteria, plasma acetic acid levels, and various health measures, including body composition, blood lipids, brain structure, and cognitive performance. We found that higher plasma acetic acid levels were associated with healthier metabolism, greater brain volume, and better cognitive abilities. These results suggest that acetic acid may serve as a link between gut health and metabolic health as well as brain function during aging, highlighting its potential as a target for future preventive strategies.
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Data availability
The data that support the findings of this study are available on request from the corresponding author, C.H.T. A decision regarding data access will be provided within four weeks of receipt of a complete request. The data are not publicly available because they contain information that could compromise research participant privacy or consent.
Code availability
The code used for data analysis in this study is not publicly available but can be provided by the corresponding author upon reasonable request.
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Acknowledgements
The phase 1 study was supported by a grant CORPG3J0371 from Chang Gung Memorial Hospital. The phase 2 study was supported by grant XMRPG3L102 from Chang Gung Memorial Hospital, sponsored by Wang Chang Gung Charity Trust. The authors acknowledge the data collection, data management, and information technology services, based on the Structured Research and Medical Informatics Cloud (SRMIC) platform system, provided by the Clinical Trial Center, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C., with support by the Ministry of Health and Welfare under Grant No. MOHW110-TDU-B-212-124005. The funders had no role in study design, data collection and analysis, preparation of the paper, or the decision to publish.
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T.Y.S. and C.H.T. conceived and designed the study. T.Y.S., C.H.T., J.T.F., C.H.C., Y.M.Y., M.L.C., C.J.L., A.M.C.W., S.N.L., and C.P.L. acquired, analyzed, or interpreted data. T.Y.S. and C.H.T. drafted the manuscript. All authors critically revised the manuscript for important intellectual content. T.Y.S. and C.H.T. performed statistical analysis. J.T.F. obtained funding.
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Communications Medicine thanks Theis Lange and Anja Lok for their contribution to the peer review of this work.
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Siow, T.Y., Wong, A.MC., Fang, JT. et al. Plasma acetic acid mediates the relationship between gut microbiome and various health measures in older adults. Commun Med (2026). https://doi.org/10.1038/s43856-026-01566-x
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DOI: https://doi.org/10.1038/s43856-026-01566-x
