Tuesday, January 6, 2026 1/6/2026

Mechanisms of Fecal Microbiota Transplant Protection from Recurrent C. difficile

Award Number: R01AI152477
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: 07/24/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2029

Group Awards By:

View Award Description

Mechanisms of Fecal Microbiota Transplant Protection from Recurrent C. difficile - Project Summary Introduction: Recurrent C. difficile infection (rCDI) occurs in one of every five patients infected. The most effective therapy is fecal microbiota transplant (FMT). Here we propose to understand how FMT acts to protect patients with rCDI through colon biopsies pre- and post-FMT, and through mouse models of FMT. Hypothesis: FMT prevents recurrent CDI (rCDI) by: (1) decreasing SNS signaling via α2AR; (2) activating ILC2; and (3) mediating intestinal epithelial proliferation and repair via EGFR. Significance: Successful completion of the work will identify mechanisms of action of FMT, which is the most effective therapy for rCDI, and will lay the foundation for therapy for rCDI targeting the SNS, immune system and/or EGFR as an adjunct and/or replacement for FMT. In addition the work has potential applications in other diseases where FMT is being applied including inflammatory bowel disease and cancer checkpoint inhibitor resistance. Investigators: The MPIs William Petri and Girija Ramakrishnan have collaborated and co-published for over 25 years and together have set the stage for the proposed studies through a clinical study of humans undergoing FMT for rCDI, and through mechanisms of action studies of CDI and FMT in mouse models. Innovation: The hypothesis is innovative as it challenges, by its exploration of FMT impact on the host, the existing paradigm that FMT acts predominantly by its impact on the pathogen C. difficile. Innovative approaches include the longitudinal study of subjects undergoing FMT for rCDI, transgenic mouse models to probe the actions of the SNS, ILC and EGFR in rCDI and FMT, and innovative techniques including spatial transcriptomics and scRNAseq of the colon. Progress over the last 5 years of funding: Includes the discoveries that the TNFα and IL-8 response to CDI in the mouse model is initiated by a2AR activation; that IL-33 acts via ILC2 in mice to block Th17 and promote anti-TcdB antibody production; and that in humans FMT increased amphiregulin, crypt depth and Myc and mTOR signaling. There have been 15 peer-reviewed original research papers, 3 preprints, and 3 reviews over the 5-year funding period supported by 5R01AI152477 and two patent filings. Approach: In each Aim a mouse model of FMT will be compared to humans undergoing FMT. Speciﬁc Aim 1: Test if FMT prevents CDI damage by downregulating the SNS. Speciﬁc Aim 2: Test if FMT decreases inflammation by activating ILC2 Speciﬁc Aim 3: Test if FMT repairs the gut via EGFR Environment: The University of Virginia Division of Infectious Diseases and Beirne Carter Immunology Center provide a rich intellectual environment in the Carter-Harrison Medical Research Building where the work will be conducted.


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	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	6	11/21/2025	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $3,202,592 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	6	7/14/2025	COMPETING CONTINUATION	$3,202,592
														Subtotal = $3,202,592

Issue Date FY: 2024 ( Subtotal = $775,719 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	5	6/17/2024	NON-COMPETING CONTINUATION	$775,719
														Subtotal = $775,719

Issue Date FY: 2023 ( Subtotal = $783,404 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	4	6/22/2023	NON-COMPETING CONTINUATION	$783,404
														Subtotal = $783,404

Issue Date FY: 2022 ( Subtotal = $784,076 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	3	6/24/2022	NON-COMPETING CONTINUATION	$784,076
2022	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	2	5/24/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $784,076

Issue Date FY: 2021 ( Subtotal = $781,166 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	2	7/2/2021	NON-COMPETING CONTINUATION	$781,166
														Subtotal = $781,166

Issue Date FY: 2020 ( Subtotal = $767,972 )
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	1	7/23/2020	NEW	$767,972
														Subtotal = $767,972

Grand Total All Awards = $7,094,929

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of Fecal Microbiota Transplant Protection from Recurrent C. difficile

Award Number: R01AI152477

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: 07/24/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer