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Effect of an Anti-Inflammatory Diet on Gut Homeostasis in Active and Experimental Crohn's Disease

Award Number: K01DK127008
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Effect of an Anti-Inflammatory Diet on Gut Homeostasis in Active and Experimental Crohn's Disease - Project Summary The inflammatory bowel disease (IBD) subtype, Crohn’s disease (CD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. Although the precise etiology of IBD is not known, evidence suggests that environmental factors, including diet, contribute to its pathogenesis.1-3 Specifically, dietary amino acids serve as key regulatory factors in cellular and microbial metabolic pathways, and disturbances in their metabolism,3 as well as altered presence of amino acid concentrations (blood/feces/urine), are observed in CD patients.4 Diet has been shown to have a pro-inflammatory effect in CD, but not much is known about anti-inflammatory diets (e.g., soy).5, 6 Gut microbial modulation via diet is a needed strategy for the therapeutic management of CD; however, no specific recommendations exist for CD patients. Moreover, studies show that the person-specific changes elicited by a dietary intervention on host immune/metabolic function reflect unique microbiota signatures. This proposal will focus on the microbiota-mediated effects of dietary soy and individual amino acid supplementation in patients with active CD compared to healthy controls. The central hypothesis of this proposal is that a soy diet induces anti-inflammatory microbiota in CD patients and that the ‘level of response’ for each individual can be predicted by metabolic and microbiome biomarkers. We will test this hypothesis directly in humans with active CD and mechanistically focus on the effect of dietary soy on the ‘pro-inflammatory potential’ of gut microbiota in CD patients. Experimentally, we will use our validated human gut microbiota SAMP1/YitFC; SAMP (hGM-SAMP) mouse model of CD-ileitis to quantify and mechanistically validate the functional effect of human feces on the severity of CD-ileitis after transplantation into GF SAMP. As a main objective, we will determine to what extent a soy-based diet could induce changes in fecal/blood inflammatory biomarkers in patients with active CD. The following aims are a continuation of our efforts to understand the microbiota-mediated effects of diet on intestinal inflammation. AIM 1: will characterize the effect of dietary soy in humans with active CD and quantify the inflammatory potential of their gut microbiome using a ‘rapid screening’ hGM-SAMP DSS-colitis model. By stratifying inflammatory microbiome/blood markers, we will identify biomarkers that could predict ‘responders’/‘non-responders’ to diet. We expect to generate a list of metabolic and microbiome clinical biomarkers that could be used to monitor response to diet in CD patients. AIM 2: will determine the impact of soy-associated amino acid dietary supplementation on the microbiome, metabolome and immunology of a spontaneous CD-like ileitis in hGM-SAMP and SPF SAMP, and AKR control mice. We will identify functional metabolic mechanisms associated with the severity of mouse CD-ileitis in response to diet. This proposal is based on strong preliminary data in mouse models of IBD that a soy-based diet treats and prevents the severity of intestinal inflammation. To translate this information to human CD represents a very significant area of investigation in this field of research and will ultimately inform the direction of future studies.


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 = $121,770 )
2025	2025	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/6/2024	NON-COMPETING CONTINUATION	$121,770
														Subtotal = $121,770

Issue Date FY: 2024 ( Subtotal = $121,770 )
2024	2024	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/12/2023	NON-COMPETING CONTINUATION	$121,770
														Subtotal = $121,770

Issue Date FY: 2023 ( Subtotal = $121,770 )
2023	2023	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/12/2022	NON-COMPETING CONTINUATION	$121,770
														Subtotal = $121,770

Issue Date FY: 2022 ( Subtotal = $121,770 )
2022	2022	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/10/2021	NON-COMPETING CONTINUATION	$121,770
														Subtotal = $121,770

Issue Date FY: 2021 ( Subtotal = $123,270 )
2021	2021	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/21/2020	NEW	$123,270
														Subtotal = $123,270

Grand Total All Awards = $610,350

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Effect of an Anti-Inflammatory Diet on Gut Homeostasis in Active and Experimental Crohn's Disease

Award Number: K01DK127008

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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