Abstract
Mild cognitive impairment (MCI) is an early stage in the progression toward dementia. Lipids are central to neurodegeneration, yet the biomarker potential of lipidomics from saliva, plasma, and feces remains underexplored. As part of the Microbiome in Aging Gut and Brain (MiaGB) consortium, saliva, plasma, and fecal samples were collected from older adults with MCI and healthy controls. Samples were analyzed by high-performance liquid chromatography coupled with high-resolution mass spectrometry (LC/MS), to profile lipidomic alterations and identify candidate biomarkers. Lipidomic profiling annotated over 200 molecular species spanning five major lipid classes. Compared with controls, MCI patients exhibited increased oxidized triacylglycerols (oxTGs) in saliva, reduced cholesteryl linoleate (CE 18:2) in plasma, and decreased fatty acid esters of hydroxy fatty acids (FAHFAs) in feces. Receiver operating characteristic (ROC) analysis identified α-linolenic acid (FA 18:3), docosapentaenoic acid (FA 22:5), and CE 18:2 as discriminatory metabolites with notable diagnostic performance. Moreover, elevated fecal triacylglycerols containing medium-chain fatty acids (TG-MCFAs) were observed in MCI, suggesting impaired lipid absorption or altered metabolism. This multi-sample lipidomics strategy highlights TG-MCFAs as fecal biomarkers for MCI detection, supporting further mechanistic and longitudinal validation.
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Acknowledgements
We would like to acknowledge the resources provided by the University of South Florida (USF) Center for Microbiome Research, the Microbiomes Institute, the Center for Excellence in Aging and Brain Repair, the Department of Neurosurgery and Brain Repair, and the USF Morsani College of Medicine.
Funding
This work was supported by the JST SPRING (Grant Number JPMJSP2119) and the Japan Society for the Promotion of Science KAKENHI Grants (25K00258 and 23K06861). Additional support was provided by the Ed and Ethel Moore Alzheimer’s Disease Research Program of the Florida Department of Health (Grant Number 22A17), as well as the U.S. National Institutes of Health, the National Institute on Aging (Grant Numbers RF1AG071762, R21AG072379, U01AG076928, and R21AG085881).
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Jayashankar Jayaprakash: methodology, data curation, visualization, writing – original draft. Siddabasave Gowda B. Gowda: conceptualization, methodology, funding acquisition, resources, visualization, supervision, writing –review and editing. Divyavani Gowda: data curation, visualization, writing – original draft. Shalini Jain: resources, writing – review and editing. Hariom Yadav: samples, resources, funding acquisition, writing – review and editing. Shu-Ping Hui: resources, writing –review and editing.
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Dr. Hariom Yadav is the cofounder and chief scientific officer of Postbiotics Inc., and BiomAge Inc. He is also cofounder of MusB LLC., MusB Research LLC., and MeraBiome Inc., with Dr. Shalini Jain. However, they have no conflict of interest with respect to the work/literature reviewed and presented in this manuscript. Other authors have no conflicts of interest to declare.
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Ethical approval was obtained from the Institutional Review Board of the University of South Florida (approval no. 002365), USA and the Ethics Committee of the Department of Health Sciences, Hokkaido University (approval no. 22–87), Japan. All methods were performed in accordance with the relevant guidelines and regulations.
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Jayaprakash, J., B. Gowda, S.G., Gowda, D. et al. Lipidomic signatures reveal biomarkers of mild cognitive impairment. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-03893-y
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DOI: https://doi.org/10.1038/s41398-026-03893-y


