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Development of targeted microbiome therapeutics and dietary interventions for potent intestinal barrier promotion to minimize GI-ARS

Award Number: U01AI172987
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/22/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Development of targeted microbiome therapeutics and dietary interventions for potent intestinal barrier promotion to minimize GI-ARS - ABSTRACT Exposure to total body irradiation (TBI) produced by nuclear accidents, premeditated nuclear, or terrorist attack causes gastrointestinal (GI) acute radiation syndrome (GI-ARS), a state of severe intestinal mucosal barrier damage, loss of tissue integrity, and translocation of the luminal content. Measures to counteract the effect of such detrimental exposure are critical for the survival and well-being of those impacted. The gastrointestinal microbiome (bacteria and metabolites) plays a crucial role in the maintenance of tissue homeostasis. Multiple studies have implicated specific microbiome clades as responsible for promoting intestinal barrier function and consequent resistance against infections and inflammatory conditions. The central hypothesis of this project is that targeted microbiome supplementation with specific subsets of intestinal bacteria or probiotics engineered to produce barrier function-promoting metabolites and their enhancement via precise dietary intervention actively improves barrier homeostasis in the intestinal epithelium, creating an environment that reduces GI-ARS. In Aim 1, we will develop novel live biotherapeutic products that minimize GI-ARS by promoting barrier function through the potent induction of functional epithelial surface P-glycoprotein expression. Additionally, we will uncover the broader distribution of this receptor system within clinical, metagenomic samples. In Aim 2, we will develop a novel genetically engineered strain of the probiotic E. coli Nissle 1917 that minimizes GI-ARS by promoting barrier function through the potent constitutive production of succinate. Lastly, in Aim 3 we will evaluate the effect of prebiotics-enriched diets in promoting GI-ARS limitation by barrier-enhancing intestinal bacteria. Cumulatively, this work will generate novel microbiome therapeutic agents that, by specifically targeting intestinal barrier function, minimize GI-ARS and increase survival after total body irradiation.


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 = $586,150 )
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	4	12/16/2025	NON-COMPETING CONTINUATION	$586,150
														Subtotal = $586,150

Issue Date FY: 2025 ( Subtotal = $568,565 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	3	12/5/2024	NON-COMPETING CONTINUATION	$568,565
														Subtotal = $568,565

Issue Date FY: 2024 ( Subtotal = $587,600 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	001	2	5/14/2024	NON-COMPETING CONTINUATION	$58,760
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	2	11/14/2023	NON-COMPETING CONTINUATION	$528,840
														Subtotal = $587,600

Issue Date FY: 2023 ( Subtotal = $601,576 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	1	12/22/2022	NEW	$601,576
														Subtotal = $601,576

Grand Total All Awards = $2,343,891

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Development of targeted microbiome therapeutics and dietary interventions for potent intestinal barrier promotion to minimize GI-ARS

Award Number: U01AI172987

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 12/22/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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