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Health promoting effects of high-polyphenol foods may be mediated through gut microbiome

Award Number: R01AT008618
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2015
PERIOD OF PERFORMANCE END DATE: 01/31/2022

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Health promoting effects of high-polyphenol foods may be mediated through gut microbiome - ¿ DESCRIPTION (provided by applicant): This multi-disciplinary and multi-institutional application aims to provide the answer to a key question in human health and nutrition: how do poorly bioavailable dietary polyphenols from fruits and vegetables lower the risk of chronic diseases, such as metabolic syndrome (MetS) and type-2 diabetes (T2D), associated with low-grade chronic inflammation. Using a high fat diet (HFD)-induced metabolic syndrome (MetS) and type-2 diabetes (T2D) murine model coupled with metagenomics and transcriptomics, we will investigate the hypothesis that poorly bioavailable dietary polyphenols from fruits and vegetables act directly in the gastrointestinal (GI) tract to remodel the gut microbiota and reduce local and systemic inflammation via interdependent mechanisms resulting in a reduction in chronic disease risk. While epidemiological, clinical and preclinical studies suggest that consumption of polyphenol-rich foods is associated with reduced risk of MetS and T2D, the mechanism(s) of protection offered by polyphenols has remained elusive due to generally poor polyphenol absorption and distribution to target tissues. Recent studies have shown that consumption of a HFD perturbs gut microbiota ecology and promotes intestinal inflammation, which precedes the development of obesity and insulin resistance characteristic of MetS/T2D. Studies in germ- free (GF; i.e. gnotobiotic) or antibiotic-treated mice demonstrated that consumption of HFD in the absence of gut microbiota protected mice from developing the clinical features of MetS/T2D, implicating the gut microbiota as a key player in the etiology of metabolic diseases. The proposed studies aim to show that poorly bioavailable polyphenols provide resilience to MetS/T2D by changing gut microbiota ecology thus reducing inflammation in the intestine. In collaboration with the laboratory of Dr. Peter Turnbaugh, a leading gut microbiota expert at Harvard University we will: 1) Use the HFD-fed C57BL/6J model of MetS/T2D to test the effects of purified polyphenol fractions from grape and cranberry on microbiome ecology, intestinal inflammation, gut barrier integrity, oral glucose tolerance and adiposity; 2) Study the dose response of polyphenols on gut microbiota and oral glucose tolerance in MetS/T2D mice and test the direct effects of polyphenols on microbiota ecology and physiology in vitro and; 3) Use antibiotic- treated MetS/T2D mice, depleted of their gut microbiota, to test direct polyphenol effects on intestinal inflammation and glucose tolerance in the absence of the gut microbiota. The proposed experiments will evaluate the host physiological and nutrigenomic responses to dietary polyphenols and relate these responses to the changes in host microbiota to provide an integrated mechanistic explanation for the health benefits of polyphenol-rich diets. Successful completion of proposed studies may substantiate the old wisdom that "an apple a day keeps the doctor away."


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: 2022 ( Subtotal = -$23,416 )
2022	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	000	5	6/29/2022	NON-COMPETING CONTINUATION	-$23,416
														Subtotal = -$23,416

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	000	5	1/25/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $387,208 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	000	5	1/18/2019	NON-COMPETING CONTINUATION	$387,208
														Subtotal = $387,208

Issue Date FY: 2018 ( Subtotal = $397,379 )
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	000	4	1/19/2018	NON-COMPETING CONTINUATION	$357,640
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	001	4	4/24/2018	NON-COMPETING CONTINUATION	$39,739
														Subtotal = $397,379

Issue Date FY: 2017 ( Subtotal = $514,050 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	002	3	7/7/2017	NON-COMPETING CONTINUATION	$50,884
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	001	3	1/4/2017	NON-COMPETING CONTINUATION	$457,955
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	000	2	12/19/2016	SUPPLEMENT FOR EXPANSION	$5,211
														Subtotal = $514,050

Issue Date FY: 2016 ( Subtotal = $444,045 )
2016	2016	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	000	2	2/1/2016	NON-COMPETING CONTINUATION	$444,045
														Subtotal = $444,045

Issue Date FY: 2015 ( Subtotal = $421,376 )
2015	2015	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research and Training in Complementary and Integrative Health	000	1	1/27/2015	NEW	$421,376
														Subtotal = $421,376

Grand Total All Awards = $2,140,642

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Health promoting effects of high-polyphenol foods may be mediated through gut microbiome

Award Number: R01AT008618

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2015

PERIOD OF PERFORMANCE END DATE: 01/31/2022

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