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Oxalobacter formigenes colonization and oxalate excretion in calcium oxalate kidney stone disease

Award Number: R01DK087967
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Calcium oxalate kidney stone disease occurs in approximately 9 % of the U.S. population and contributes significantly to health care costs. Small reductions in urinary oxalate excretion are thought to limit stone risk. Recent studies have indicated that a lack of Oxalobacter formigenes colonization is a significant risk factor for calcium oxalate kidney stone formation. Our Preliminary data shows that healthy human subjects lacking O.formigenes can be readily colonized with live preparations of O.formigenes. This ability to colonize individuals offers a powerful means of assessing responses to varying diets before and after colonization. It is still not clear under what conditions O.formigenes modifies stone risk, and much still needs to be learned about how this organism establishes and maintains gut colonization. In the previous funding cycle we identified in a mouse model conditions that influence the growth of O.formigenes in the gut, its degradation of oxalate in the gut, its effects on the amount of oxalate excreted in urine and into the intestine, and its sustainability in the absence of dietary oxalate. In this application we will extend these findings to humans by examining individuals before and after colonization with O.formigenes. Diets controlled in their contents of oxalate, calcium and other nutrients, including a diet ultra-low in oxalate, will be used to examine the interaction between diet, O.formigenes colonization and urinary oxalate excretion. This proposal will use spinach that contains carbon 13-oxalate to accurately determine whether colonization modifies the response to an oxalate-rich meal. Continuous intravenous infusions of the stable, non-radioactive oxalate isotope, 13C2- oxalate, before and after colonization will directly determine if gastrointestinal oxalate secretion occurs and whether colonization influences such secretion. Recent evidence suggests individuals are colonized with different strains and in some cases more than one strain. However, it is not known whether the biological differences between strains influence colonization persistence and urinary oxalate excretion and this will be examined in this application. If the specific aims are successfully completed they will provide valuable information about the importance of O.formigenes colonization in influencing oxalate levels, will create insight into the factors that impact O.formigenes colonization, and will help identify new strategies for modifying the gut milieu and calcium oxalate kidney stone risk.


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: 2024 ( Subtotal = -$398 )
2024	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	10/27/2023	NON-COMPETING CONTINUATION	-$398
														Subtotal = -$398

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	2/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $442,131 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	2/11/2020	NON-COMPETING CONTINUATION	$442,131
														Subtotal = $442,131

Issue Date FY: 2019 ( Subtotal = $442,131 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	3/19/2019	NON-COMPETING CONTINUATION	$442,131
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	8	5/2/2019	NON-COMPETING CONTINUATION	$0
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	4/29/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $442,131

Issue Date FY: 2018 ( Subtotal = $442,131 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	2/21/2018	NON-COMPETING CONTINUATION	$397,917
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	5/10/2018	NON-COMPETING CONTINUATION	$44,214
														Subtotal = $442,131

Issue Date FY: 2017 ( Subtotal = $442,131 )
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	1/27/2017	COMPETING CONTINUATION	$442,131
2017	2015	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	5/5/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $442,131

Issue Date FY: 2015 ( Subtotal = $319,725 )
2015	2015	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/31/2015	NON-COMPETING CONTINUATION	$0
2015	2015	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/3/2015	NON-COMPETING CONTINUATION	$319,725
														Subtotal = $319,725

Issue Date FY: 2014 ( Subtotal = $319,725 )
2014	2014	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	2/24/2014	NON-COMPETING CONTINUATION	$31,972
2014	2014	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	2/6/2014	NON-COMPETING CONTINUATION	$287,753
2014	2014	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	9/19/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $319,725

Issue Date FY: 2013 ( Subtotal = $382,835 )
2013	2013	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/23/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$20,735
2013	2013	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/27/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$287,100
2013	2013	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	9/16/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$75,000
														Subtotal = $382,835

Issue Date FY: 2012 ( Subtotal = $321,900 )
2012	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/14/2012	NON-COMPETING CONTINUATION	$321,900
2012	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/30/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $321,900

Issue Date FY: 2011 ( Subtotal = $370,000 )
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/10/2011	NEW	$321,900
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	6/13/2011	NEW	$48,100
														Subtotal = $370,000

Grand Total All Awards = $3,482,311

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Oxalobacter formigenes colonization and oxalate excretion in calcium oxalate kidney stone disease

Award Number: R01DK087967

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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