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Assessing the longitudinal impact of Mediterranean diet interventions to reduce cognitive decline on gut microbiota composition and bile acid variety

Award Number: F30AG094275
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/02/2026
PERIOD OF PERFORMANCE END DATE: 02/01/2030

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Assessing the longitudinal impact of Mediterranean diet interventions to reduce cognitive decline on gut microbiota composition and bile acid variety - PROJECT SUMMARY/ABSTRACT Alzheimer’s disease is a progressive neurodegenerative disorder with a complex etiology affecting over six million individuals in the United States alone, with numbers projected to rise significantly as the population ages. Concomitant changes in gut microbiome and metabolome composition have been observed over the course of Alzheimer’s-related cognitive decline, suggesting host microbiota may mediate the pathophysiological processes of Alzheimer’s disease and related dementias. Gut microbes contribute to host metabolism through the production and modification of metabolites, such as bile acids, which collectively influence overall metabolic health. Lifestyle interventions, such as diet modification, are promising strategies for lowering dementia risk, and these modifications are also influential in regulating the gut microbiome. However, the long-term effects of specific dietary interventions on microbially-mediated bile acid profiles and their impact on cognitive decline remain poorly understood, motivating further investigation. This proposal seeks to apply advanced computational and algorithmic approaches to identify compositional and functional changes in the gut microbiome and metabolome over the course of longitudinal dietary interventions. Aim 1 of this proposal will unify three independent cohorts assessing the impact of adherence to the Mediterranean diet, a diet high in plants and healthy fats, on cognitive decline. By conducting phylogenetically-aware metagenomic analyses and network-based untargeted metabolomic analyses, this proposal aims to identify changes in microbial communities and bile acid profiles during Mediterranean dietary interventions, and correlate these changes with host phenotypes indicative of Alzheimer’s risk. Complementarily, Aim 2 of this proposal will assess the prognostic potential of gut microbiome and metabolome features by constructing and evaluating machine learning models to predict cognitive outcomes over the course of intervention. These efforts will deepen our understanding of the relationship between diet, the gut microbiome, bile acid proliferation, and cognitive health by employing standardized and reproducible methodological analyses across large cohorts. Ultimately, this research is poised to reveal mechanistic targets for future study, facilitating the development of novel diagnostic and therapeutic strategies for Alzheimer's disease in at-risk populations.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $43,784 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Aging Research	002	1	3/31/2026	NEW	$576
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Aging Research	001	1	2/2/2026	NEW	$0
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Aging Research	000	1	2/2/2026	NEW	$43,208
														Subtotal = $43,784

Grand Total All Awards = $43,784

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Assessing the longitudinal impact of Mediterranean diet interventions to reduce cognitive decline on gut microbiota composition and bile acid variety

Award Number: F30AG094275

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/02/2026

PERIOD OF PERFORMANCE END DATE: 02/01/2030

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