Wednesday, January 28, 2026 1/28/2026

Gut Microbiota and Cardiometabolic Diseases

Award Number: P01HL147823
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Gut Microbiota and Cardiometabolic Diseases - Gut Microbiota and Cardiometabolic Diseases. Abstract: The overarching mission of our Program is to generate critical scientific discoveries in the field of gut microbiome and cardiometabolic diseases that lead to potential improvements in human health, wellbeing, and patient care. Substantial evidence has accrued demonstrating a critical role for gut microbiota in both human health and disease. Our Program will advance the concept of metaorganismal endocrinology – specifically – that gut microbes organize to form a key endocrine organ that converts nutritional cues from the environment into hormone-like signals that impact cardiovascular and metabolic phenotypes in the human host. Our Program is comprised of 3 Projects and 4 Cores. Project 1, seeks to discover and functionally interrogate novel gut microbial pathways linked to the development of CVD and its adverse events, with initial focus on the metaorganismal PhenylAcetyGlutamine (PAGln) pathway. Preliminary studies show PAGln is gut microbiota generated metabolite whose levels are strikingly linked to CVD that through numerous preliminary cellular, microbiota and animal model studies, contributes to CVD pathogenesis. Analytical, biochemical and disease model studies in mice and humans explore the functional impact of PAGln on in vivo thrombosis and atherosclerosis. Project 2 is thematically linked to Projects 1 and 3, and tests the hypothesis that the gut microbial co-metabolites TMA and TMAO are unique hormone-like drivers of high fat diet induced obesity and atherosclerosis. Through use of tools generated with Project 1 and 3, the role of microbial choline TMA lyase activity in enhancing susceptibility for high fat diet-driven obesity via a host TMA - Taar5 receptor signaling axis will be tested. The hypothesis that FXR-driven hepatobiliary secretion of TMAO initiates a newly discovered enterohepatic TMAO signaling axis that regulates gut microbiome community structure and host bile acid/sterol metabolism will also be explored. Project 3 is similarly interrelated to Projects 1 and 2, and leverages both human untargeted metabolomics data collaboratively discovered with Project 1, animal cardiometabolic disease phenotyping expertise of Project 2 investigators, and metabolic pathway discovery and microbiome gene editing expertise of Project 3 investigators to enabled studies of causality and mechanism for structurally specific members of two key classes of gut microbe-derived molecules, aryl sulfates and secondary bile acids. The role of specific microbial genes responsible for forming candidate CVD- and diabetes-associated metabolites will be examined for their involvement in enhanced thrombosis, atherosclerosis, obesity and other metabolic phenotypes. Four cores (Analytical/Clinical/Bioinformatics; Analytical and Chemical Synthesis; Microbial Engineering and Transplantation; and Cardiometabolic Disease Phenotyping) provide multi-project support, significantly strengthening the research Program. The proposed Program Project will yield greater understanding of the participation of the gut microbiome in cardiometabolic diseases, and help advance our long-term goal of developing potential improvements in human health, wellbeing, and patient care.


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 = -$14,527 )
2026	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	000	5	1/19/2026	NON-COMPETING CONTINUATION	-$14,527
														Subtotal = -$14,527

Issue Date FY: 2023 ( Subtotal = $2,425,292 )
2023	2023	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	000	5	7/12/2023	NON-COMPETING CONTINUATION	$2,425,292
														Subtotal = $2,425,292

Issue Date FY: 2022 ( Subtotal = $2,423,889 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	000	4	6/24/2022	NON-COMPETING CONTINUATION	$2,423,889
														Subtotal = $2,423,889

Issue Date FY: 2021 ( Subtotal = $2,423,889 )
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	000	3	7/7/2021	NON-COMPETING CONTINUATION	$2,423,889
														Subtotal = $2,423,889

Issue Date FY: 2020 ( Subtotal = $2,423,889 )
2020	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	000	2	6/30/2020	NON-COMPETING CONTINUATION	$2,423,889
														Subtotal = $2,423,889

Issue Date FY: 2019 ( Subtotal = $2,445,300 )
2019	2019	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Cardiovascular Diseases Research	000	1	8/29/2019	NEW	$2,445,300
														Subtotal = $2,445,300

Grand Total All Awards = $12,127,732

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Gut Microbiota and Cardiometabolic Diseases

Award Number: P01HL147823

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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