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Lipidomic signatures reveal biomarkers of mild cognitive impairment
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  • Published: 16 February 2026

Lipidomic signatures reveal biomarkers of mild cognitive impairment

  • Jayashankar Jayaprakash1,
  • Siddabasave Gowda B. Gowda  ORCID: orcid.org/0000-0002-7972-99821,2,
  • Divyavani Gowda2,
  • MiaGB Consortium,
  • Shalini Jain3,4,
  • Hariom Yadav3,4 &
  • …
  • Shu-Ping Hui2 

Translational Psychiatry , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diagnostic markers
  • Neuroscience

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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Data availability

All data relevant to the study are contained within the article and supplementary information.

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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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Authors and Affiliations

  1. Graduate School of Global Food Resources, Hokkaido University, Kita-9, Nishi-9, Kita-Ku, Sapporo, 060-0809, Japan

    Jayashankar Jayaprakash & Siddabasave Gowda B. Gowda

  2. Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, 060-0812, Japan

    Siddabasave Gowda B. Gowda, Divyavani Gowda & Shu-Ping Hui

  3. Microbiome in aging Gut and Brain (MiaGB) consortium, USF Center for Microbiome Research, Microbiomes Institute, University of South Florida, 3515 E Fletcher Avenue, Tampa, FL, 33612, USA

    Hariom Yadav, Shalini Jain, Amanda Smith, Ambuj Kumar, Corinne Labyak, Michal Masternak, Peter J. Holland, Marc E. Agronin, Andrea Y. Arikawa, Cynthia White-Williams, Shalini Jain & Hariom Yadav

  4. USF Center for Microbiome Research, Microbiomes Institute, University of South Florida, 12901 Bruce B Downs, MDC78, Tampa, FL, 33612, USA

    Shalini Jain & Hariom Yadav

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  1. Jayashankar Jayaprakash
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MiaGB Consortium

  • Hariom Yadav
  • , Shalini Jain
  • , Amanda Smith
  • , Ambuj Kumar
  • , Corinne Labyak
  • , Michal Masternak
  • , Peter J. Holland
  • , Marc E. Agronin
  • , Andrea Y. Arikawa
  •  & Cynthia White-Williams

Contributions

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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Correspondence to Siddabasave Gowda B. Gowda or Hariom Yadav.

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Competing interests

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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  • Received: 29 August 2025

  • Revised: 19 December 2025

  • Accepted: 30 January 2026

  • Published: 16 February 2026

  • DOI: https://doi.org/10.1038/s41398-026-03893-y

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