Microbiota, metabolites, and colon neoplasia

Active Project Grant Awarded Last action

Award ID
R01CA252045
Recipient
Awarding agency
Obligated
$6,310,397

Award facts

Assistance listing
93.393 Cancer Cause and Prevention Research
Completion date 91% complete
Originally
Funding
  • $5,599,975.00 Federal
  • $710,422.00 Non-federal
Place of performance
Farmington, CT 06032, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The human diet can positively or negatively impact cancer incidence, with plant-derived compounds - such as polyphenols - often exhibiting antioxidant cancer-preventive properties. Walnuts are an exceptional source of polyphenolic ellagitannins (ETS) that are converted to ellagic acid and various urolithins by GUT microbiota in the colon. Urolithin a (uroa) is of particular interest for its potent anti-cancer, anti-inflammatory, and prebiotic activities. However, uroa production in individuals can vary significantly, likely based on differences in GUT microbiota. We will substantiate the anti-cancer benefits of a prebiotic/probiotic complex derived from consuming walnuts and determine the basis of human inter-individual variability in uroa formation. Our overall hypothesis is that walnut supplementation improves colonic health and lowers colorectal cancer (CRC) risk through uroa formation. This leads to several working hypotheses guiding our aims: working hypothesis 1. Uroa producers are at a lower risk of having an advanced colonic lesion; working hypothesis 2. Walnut supplementation will increase urinary uroa levels; and working hypothesis 3. CRC prevention by walnuts will be greater in uroa-producers than in non-producers. In aim 1, we propose a randomized, controlled crossover trial in 69 patients (45-75 y) to examine walnut effects on CRC risk factors. We will associate an individual's ability to produce uroa with biomarkers of inflammation and CRC risk, and identify the bacterial species responsible for urolithin metabolism. In aim 2, we will investigate prebiotic effects of ET-containing walnuts in two conditional mouse CRC models, focusing on important processes in CRC and inflammation, including bile acid metabolism, inflammation, and short chain fatty acid production. In aim 3, we will test the probiotic effects of human uroa-producing microbiota in a mouse fecal microbiota transplant (MT) study and demonstrate a causal role for specific microbes in uroa formation. This will enable US to validate the concept that important protective effects of walnuts and other ET-rich foods occur through specific microbiota-derived metabolites. This will also define biomarkers and probiotics that highlight the benefits of these foods. Our approach incorporates personalized nutrition with a focus on uroa producers and non-producers in colonic health. Ultimately, our human and pre-clinical mouse studies may lead to prebiotics and probiotics that increase protective urolithins for CRC prevention. These highly significant studies will test the ability of the microbiota to generate colonic mucosa-protective agents (e.g., uroa). IT is possible that high-risk patients can be efficiently converted to a protective state by taking probiotics to realize the full benefits of ET-rich foods.

Transactions

Action Federal Non-federal Date
Amendment $0 $0
Amendment $57,531 $0
Amendment $57,531 $0
Amendment $517,782 $0
Amendment $517,782 $0
Amendment $557,628 $0
Amendment $557,628 $0
Amendment $631,851 $0
Amendment $631,851 $0
Amendment $649,547 $0
Amendment $710,422 $0
Original award $710,422 $710,422
Show all 12

Subawards

Subrecipient Amount Awarded
University Of Connecticut As a Co-Investigator, I will collaborate with UConn Health on a project, entitled “Microbiota, Metabolites, and Colon Neoplasia." The primary goal of the… $21,407
Weill Medical College Of Cornell University Weill Medical College will participate in recruitment of patients for the clinical trial for Microbiota, Metabolites, and Colon Neoplasia. We will coordinate… $22,415
University Of Florida The PI and his team at the University of Florida will take the overall responsibility for the planning and conducting of the studies described in aim 1 “Human… $164,335
Agencia Estatal Consejo Superior De Investigaciones Cientificas Our group (Food & Health Lab; Research Group on Quality, Safety, and Bioactivity of Plant Foods; CEBASCSIC, Murcia, Spain) is worldwide known for pioneering the… $1,539
University Of Connecticut As a Co-Investigator, I will collaborate with Dr. Daniel Rosenberg on a project, entitled "Microbiota, Metabolites, and Colon Neoplasia." The primary goal of… $15,802
Weill Medical College Of Cornell University We will participate in recruitment of patients for the clinical trial for Microbiota, Metabolites, and Colon Neoplasia. We will coordinate statistical… $22,415
University Of Florida Dr. Christian Jobin and his team at the University of Florida will take the overall responsibility for the planning and conducting of the studies described in… $168,900

Quick answers

Who received award R01CA252045?

R01CA252045 was awarded to University Of Connecticut Health Center by National Cancer Institute (National Institutes of Health) on May 1, 2021.

How much is award R01CA252045 worth?

$6,310,397 has been obligated on R01CA252045: $5,599,975 in federal funding and $710,422 in non-federal funding.

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