Brain Health and the Gut Microbiome (bMicrobiome Study): A Proof-of-Concept, Feasibility Study Integrating Shotgun Metagenomics, Metrology, and Multidimensional Phenotyping Across the Cognitive Aging Spectrum

Published

June 9, 2026

Author(s)

Leigh Frame, Alison Warren, Abdelmohsen Al Qalam, Patrick Corr, Mina Farah, Michaela Karam, Katherine Rangoussis, Mehrshad Fahim Devin, Zeynep Celikkol, Lindsey Gordon, Daniel Villarreal, Elizabeth Catto, Yvonne Udam, Katherine Thompson, Owen Lubinski, Abdallah Samman, Alia Badawi, Holly Hack, Monique Hunter, Ian Hines, Stephanie Servetas, Scott Jackson, Nur A Hasan, Mikhail Kogan

Abstract

Background: Gut microbiome alterations have been associated with cognitive decline inconsistently, owing to insufficient power, methodological variability, limited integration of behavioral and lifestyle factors, etc. Methods: This prospective, proof-of-concept study integrated multidimensional phenotyping with metagenomic sequencing (shotgun) in adults (50–90 years) around Washington, DC. Participants were classified as healthy controls (HC) or mild cognitive impairment (MCI) by clinical history; early Alzheimer's disease (eAD) participants were unable to complete study requirements. Longitudinal assessment used Boston Cognitive Assessment (BoCA), patient-reported outcomes (PROMIS-29), dietary intake and quality (DietID™), readiness-for-change (adapted URICA), at-home stool sample collection. Results: Seventeen participants completed sufficient assessments (HC n=11; MCI n=6). Substantial overlap in gut microbiome composition was observed between HC and MCI. Poorly characterized or uncommon taxa drove trends; unassigned taxa were common. Assessment revealed high diet quality and variability in dietary patterns and key components (vegetables, whole grains, fat, fish). Participants demonstrated high readiness to engage in nutritional behavior change, with individuals with MCI reporting greater concern about maintaining changes and stronger desire for external support. Conclusions: Integrating multidimensional phenotyping with metagenomics is feasible in cognitive decline. Findings highlight biological and behavioral heterogeneity, limitations of species-level inference, and diet and behavioral readiness as modifiable contextual factors.

Citation

Gut Microbes Reports

Pub Type

Journals

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Keywords

gut microbiome, cognitive aging, mild cognitive impairment, Alzheimer’s disease, gut-brain axis, shotgun metagenomics, metrology, precision nutrition

Citation

Frame, L. , Warren, A. , Al Qalam, A. , Corr, P. , Farah, M. , Karam, M. , Rangoussis, K. , Fahim Devin, M. , Celikkol, Z. , Gordon, L. , Villarreal, D. , Catto, E. , Udam, Y. , Thompson, K. , Lubinski, O. , Samman, A. , Badawi, A. , Hack, H. , Hunter, M. , Hines, I. , Servetas, S. , Jackson, S. , Hasan, N. and Kogan, M. (2026), Brain Health and the Gut Microbiome (bMicrobiome Study): A Proof-of-Concept, Feasibility Study Integrating Shotgun Metagenomics, Metrology, and Multidimensional Phenotyping Across the Cognitive Aging Spectrum, Gut Microbes Reports, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=961623 (Accessed September 2, 2026)

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