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Host-Microbiota-Diet Interactions in Metabolic Syndrome and IBD

Award Number: R01DK083890
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2010
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Host-Microbiota-Diet Interactions in Metabolic Syndrome and IBD - Humanity is increasingly afflicted by chronic inflammatory diseases, including inflammatory bowel disease (IBD) and metabolic syndrome (Met Syn), which collectively refers to the constellation of metabolic problems associated with obesity. The grant this application seeks to renew has developed our hypothesis that IBD and Met Syn share commonalities of disease pathophysiology, namely that poor management of gut microbiota plays a key role in driving inflammation that is central to both disease states. A central feature of the microbiota dysbiosis observed in both IBD and Met Syn is a more “aggressive” microbiota that encroaches upon the gut epithelium, which is likely germane to its promotion of inflammation. One means of inducing microbiota encroachment and its inflammatory consequences is via consumption of a diet lacking fermentable fiber. We found that such low fiber diet-induced encroachment involves ablation of microbiota-mediated innate lymphoid cell (ILC) IL-22 production that normally serves to fortify the epithelium. Consequently, enriching such diets with the fermentable fiber inulin, but not the insoluble/non-fermentable fiber cellulose, restored IL-22 production, reduced microbiota encroachment, ameliorated low-grade inflammation, and protected mice from diet-induced Met Syn. However, we’ve also observed that enriching refined diets with some fermentable fibers also induced some IL-22-independent negative consequences, including exacerbating experimentally-induced colitis and promoting liver cancer thus highlighting that, at present, we lack the knowledge to safely engineer health-promoting foods. Hence, our central overall hypothesis is that better mechanistic understanding of how dietary fiber impacts the host-microbiota relationship will inform efforts to design diets and/or more safely and effectively engineer foods that promote beneficial intestine-microbiota interactions, thus ameliorating gut inflammation and its associated disease states, including IBD and Met Syn. We will investigate this hypothesis via 3 specific aims: Aim 1: Identify means by which nourishing microbiota with fiber results in ILC-mediated IL-22 production. Aim 2: Define mechanism underlying psyllium’s ability to protect against metabolic syndrome and colitis. Aim 3: Develop a means of targeted delivery of colonic IL-22 and investigate its ability to restore gut health and ameliorate inflammatory diseases.


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 = $0 )
2025	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	5/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $522,819 )
2023	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	1/12/2023	NON-COMPETING CONTINUATION	$522,819
														Subtotal = $522,819

Issue Date FY: 2022 ( Subtotal = $522,819 )
2022	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	1/11/2022	NON-COMPETING CONTINUATION	$470,536
2022	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	12	3/28/2022	NON-COMPETING CONTINUATION	$52,283
														Subtotal = $522,819

Issue Date FY: 2021 ( Subtotal = $521,900 )
2021	2021	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	2/3/2021	NON-COMPETING CONTINUATION	$52,190
2021	2021	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	11/17/2020	NON-COMPETING CONTINUATION	$469,710
														Subtotal = $521,900

Issue Date FY: 2020 ( Subtotal = $533,139 )
2020	2020	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	12/27/2019	COMPETING CONTINUATION	$533,139
														Subtotal = $533,139

Issue Date FY: 2018 ( Subtotal = $340,875 )
2018	2018	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	8/14/2018	NON-COMPETING CONTINUATION	$340,875
														Subtotal = $340,875

Issue Date FY: 2017 ( Subtotal = $340,875 )
2017	2017	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	8/18/2017	NON-COMPETING CONTINUATION	$340,875
														Subtotal = $340,875

Issue Date FY: 2016 ( Subtotal = $340,875 )
2016	2016	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	8/18/2016	NON-COMPETING CONTINUATION	$340,875
														Subtotal = $340,875

Issue Date FY: 2015 ( Subtotal = $338,625 )
2015	2015	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	5/19/2015	COMPETING CONTINUATION	$338,625
														Subtotal = $338,625

Issue Date FY: 2014 ( Subtotal = $296,839 )
2014	2014	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	3/4/2014	NON-COMPETING CONTINUATION	$29,683
2014	2014	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/18/2013	NON-COMPETING CONTINUATION	$267,156
														Subtotal = $296,839

Issue Date FY: 2013 ( Subtotal = $286,450 )
2013	2013	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/12/2012	NON-COMPETING CONTINUATION	$267,156
2013	2013	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	5/23/2013	NON-COMPETING CONTINUATION	$19,294
														Subtotal = $286,450

Issue Date FY: 2012 ( Subtotal = $267,705 )
2012	2012	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	1/9/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$240,935
2012	2012	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION	33 GILMER STREET SOUTHEAST	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	2/3/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$26,770
2012	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/5/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $267,705

Issue Date FY: 2011 ( Subtotal = $318,409 )
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/22/2010	NON-COMPETING CONTINUATION	$289,463
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/24/2011	NON-COMPETING CONTINUATION	$28,946
														Subtotal = $318,409

Issue Date FY: 2010 ( Subtotal = $387,500 )
2010	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/13/2010	NEW	$387,500
														Subtotal = $387,500

Grand Total All Awards = $5,018,830

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Host-Microbiota-Diet Interactions in Metabolic Syndrome and IBD

Award Number: R01DK083890

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2010

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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