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Exacerbation of Colitis by Enterobacteriaceae

Award Number: R01AI112445
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: 01/15/2015
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Exacerbation of Colitis by Enterobacteriaceae - ABSTRACT Ulcerative colitis is a complex disease caused by a combination of genetic risk factors, childhood exposure to environmental risk factors and a poorly defined microbiota component. Ulcerative colitis is associated with imbalance in the microbiota (dysbiosis) characterized by increased Enterobacteriaceae and reduced Clostridia abundance. Ulcerative colitis can respond to antibiotic treatment, which suggests that dysbiosis exacerbates intestinal inflammation, thus raising the question as to how microbiota homeostasis can be restored. Our preliminary data suggest that epithelial hypoxia and epithelial release of hydrogen peroxide represent host control mechanisms that maintain homeostasis in the colon and that facultative anaerobic Enterobacteriaceae exacerbates colitis when these host control mechanisms become weakened by a combination of genetic and environmental risk factors. Our central hypothesis is that increased epithelial oxygenation drives an expansion of facultative anaerobic Enterobacteriaceae that exacerbate colitis because members of this family are not excluded by growth conditions encountered in close proximity to the epithelial surface. In specific aim 1 we will test the working hypothesis that rebalancing the gut microbiota by reinstating epithelial hypoxia represents a feasible approach for restoring gut homeostasis. In specific aim 2 we will determine how Enterobacteriaceae exacerbate colitis in mice carrying a genetic risk factor while being exposed to a combination of environmental risk factors. Successful completion of the proposed work will be of broad significance for research on microbial ecology in the gut, the dynamics of gut- associated microbial communities during inflammation and the pathogenesis of ulcerative colitis.


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: 2025 ( Subtotal = $432,475 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	10	4/16/2025	NON-COMPETING CONTINUATION	$432,475
														Subtotal = $432,475

Issue Date FY: 2024 ( Subtotal = $442,713 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	9	4/3/2024	NON-COMPETING CONTINUATION	$442,713
														Subtotal = $442,713

Issue Date FY: 2023 ( Subtotal = $452,573 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	8	2/24/2023	NON-COMPETING CONTINUATION	$452,573
														Subtotal = $452,573

Issue Date FY: 2022 ( Subtotal = $461,954 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	7	3/21/2022	NON-COMPETING CONTINUATION	$461,954
														Subtotal = $461,954

Issue Date FY: 2021 ( Subtotal = $471,000 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	6	4/13/2021	COMPETING CONTINUATION	$471,000
														Subtotal = $471,000

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	5	5/12/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $392,500 )
2019	2019	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	5	12/14/2018	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2018 ( Subtotal = $392,500 )
2018	2018	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	4	12/20/2017	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2017 ( Subtotal = $392,500 )
2017	2017	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	3	12/2/2016	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2016 ( Subtotal = $391,875 )
2016	2016	UNIVERSITY OF CALIFORNIA	1850 RESEARCH PARK DRIVE	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	2	12/3/2015	NON-COMPETING CONTINUATION	$391,875
														Subtotal = $391,875

Issue Date FY: 2015 ( Subtotal = $390,000 )
2015	2015	UNIVERSITY OF CALIFORNIA	1850 RESEARCH PARK DRIVE	DAVIS	CA	95618	YOLO	USA	Allergy and Infectious Diseases Research	000	1	1/7/2015	NEW	$390,000
														Subtotal = $390,000

Grand Total All Awards = $4,220,090

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Exacerbation of Colitis by Enterobacteriaceae

Award Number: R01AI112445

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: 01/15/2015

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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