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Investigating Immune-Microbiome interactions during treatment of Clostridioides difficile with fecal microbiome transplantation

Award Number: R01AI158830
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/05/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Investigating Immune-Microbiome interactions during treatment of Clostridioides difficile with fecal microbiome transplantation - Project Summary Hospitalized patients receiving antibiotic treatment experience a disruption in the intestinal microbiome enabling opportunistic pathogens, such as Clostridioides difficile to colonize the intestinal tract. Complications resulting from C. difficile associated disease are a major burden on the health care system costing an estimated one billion dollars and resulting in 12,000-20,000 deaths per year (11, 13). Current antibiotic treatment options have a high recurrence rate highlighting the need to develop alternative treatment strategies. Fecal microbiome transplantation (FMT) has proven to be a remarkable effective strategy for treatment of recurrent C. difficile infection (21). However, the host and microbial factors that contribute to FMT success remain poorly defined. The murine model of C. difficile infection offers insights into the mechanism of action of FMT. Data presented in this proposal demonstrates an important role for the host’s immune system, specifically CD4+ T-regulatory (TReg) cells, in supporting FMT efficacy. In aim 1 of this proposal we will investigate the immunoregulatory mechanisms through which TReg cells shape the intestinal environment to promote FMT engraftment and C. difficile resolution. Conversely, aim 2, will assess the innate immune inflammatory mediators that shape the intestinal environment to inhibit FMT engraftment and C. difficile resolution. In parallel to murine studies, we will conduct longitudinal profiling of human immune cell populations in severe C. difficile infected patients before and after FMT. These aims will identify immune mechanisms that support successful FMT therapy in C. difficile infection and potentially identify novel therapeutic targets in treating C. difficile associated disease. 1


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 = $0 )
2026	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	5	11/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $468,900 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	5	2/13/2025	NON-COMPETING CONTINUATION	$468,900
														Subtotal = $468,900

Issue Date FY: 2024 ( Subtotal = $468,900 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	4	5/28/2024	NON-COMPETING CONTINUATION	$46,889
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	4	1/4/2024	NON-COMPETING CONTINUATION	$422,011
														Subtotal = $468,900

Issue Date FY: 2023 ( Subtotal = $468,900 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	3	1/5/2023	NON-COMPETING CONTINUATION	$468,900
														Subtotal = $468,900

Issue Date FY: 2022 ( Subtotal = $476,150 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	1/12/2022	NON-COMPETING CONTINUATION	$476,150
														Subtotal = $476,150

Issue Date FY: 2021 ( Subtotal = $474,349 )
2021	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	2/5/2021	NEW	$474,349
														Subtotal = $474,349

Grand Total All Awards = $2,357,199

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Investigating Immune-Microbiome interactions during treatment of Clostridioides difficile with fecal microbiome transplantation

Award Number: R01AI158830

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/05/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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