Source: UNIV OF MARYLAND submitted to
GUT MICROBIAL METABOLITES OF APPLE POLYPHENOLS: INTERROGATING INDIVIDUAL DIFFERENCES TO ESTABLISH FUNCTIONAL BIOMARKER UTILITY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
NEW
Funding Source
Reporting Frequency
Annual
Accession No.
1031146
Grant No.
2022-67017-41032
Project No.
MD-NFSC-05787
Proposal No.
2023-05787
Multistate No.
(N/A)
Program Code
A1343
Project Start Date
Oct 1, 2023
Project End Date
Jun 30, 2025
Grant Year
2023
Project Director
Slavin, M.
Recipient Organization
UNIV OF MARYLAND
(N/A)
COLLEGE PARK,MD 20742
Performing Department
(N/A)
Non Technical Summary
Flavonoids are a class of chemical compounds that are present in a variety of plant foods and are widely accepted to have health benefits, including reducing risk of cardiovascular disease. However, there are differences in how individual people respond to consuming dietary flavonoids, which current science is unable to fully explain. It is possible that differences in the types or activities of bacteria in the gut may influence how flavonoids are absorbed into the bloodstream, and therefore may explain the different health benefits experienced by people after eating them.This study seeks to explain part of this variation. People with two distinct patterns of a gut bacteria activity will be fed a diet that is controlled in catechins (a specific type of flavonoid) by providing a controlled amount of apple juice. Apples are a commonly consumed source of catechins in the American diet. Study participants' urine will be monitored to determine whether individuals are absorbing different forms of catechins as a result of gut bacteria actions, and their feces will be monitored to determine any relationship with specific bacteria that are present in the gut.If successful, the project will identify an easily accessible urinary biomarker capable of predicting who will have different responses to consuming dietary flavonoids. This result could then be explored in further studies to determine if it predicts cardiovascular health benefits of the catechins and other flavonoids. Ultimately, this work could lead to designing targeted diets for individuals based on a combination of biomarker status and disease risk.
Animal Health Component
0%
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70211101010100%
Goals / Objectives
The overall goal of this project is to evaluate the potential for O-desmethylangolensin (ODMA) to serve as a biomarker of gut microbial metabolic functionality for cleavage of the flavonoid C-ring. The project will achieve this through the following objectives:Identify a group of 15 ODMA non-producers and 15 ODMA producers, matched on personal characteristics.Quantify differences in urinary microbial catechin metabolite excretion across individuals based on ODMA metabotype.Characterize microbiome components associated with catechin metabolism and changes in gut microbiome associated with a high-catechin diet.
Project Methods
Efforts:The project will recruit 300 adult participants and screen them for having a gut microbial community capable of producing ODMA from daidzein by feeding them a soy food snack (source of dietary daidzein) for 3 days, followed by measuring ODMA in their urine. Participants will also complete surveys on their usual dietary habits and general health information. Fifteen participants who do not have ODMA in their urine (ODMA non-producers) will be recruited to participate in a subsequent randomized block crossover design clinical trial, along with 15 age- and gender-matched participants who do have ODMA in their urine (ODMA producers). During the clinical trial, the participants will be asked to consume a controlled diet for two 3-day phases separated by a 10-day wash out period, which will consist of a low-catechin control phase and an apple juice phase that provides a known moderate amount of catechins per day. The order of the phases will be randomized within blocks of ODMA producers and non-producers. Urine and fecal samples will be collected before and after each phase, and additional data on dietary intake will be collected in the time period leading up to and during each phase. Urine samples will be analyzed for microbial metabolites of catechins, and fecal samples will undergo metagenomic analysis.Evaluation:Statistical analyses will be conducted to: 1) compare microbial catechin metabolite levels in ODMA non-producers vs. ODMA producers to quantifying differences in microbial catechin metabolite production in ODMA producers vs. non-producers; 2) compare community composition of the gut microbiome associated with microbial metabolite production to identify gut microbial characteristics associated with microbial catechin metabolite production. Further analysis will explore the impact of catechin ingestion on gut microbial composition and differences in gut microbiome characteristics associated with ODMA non-producers vs. ODMA producers.

Progress 10/01/23 to 09/30/24

Outputs
Target Audience:The target audience engaged during this period was potential research participants, engaged as part of the recruitment process. This includesadults, aged 18-45 years old in Prince Georges County, Maryland, and neighboring counties. These individuals were recruited to participate in the research study by a variety of means, including paper flyers on and near campus, targeted and untargeted social media campaigns, emails to departments, groups and organizations on campus,posts on research recruiting websites, and our own study website. We have also engaged with the research community on the campus of the University of Maryland, advertising the study to scientific organizations on campus, and involving graduate and undergraduate students in the research process. Changes/Problems:We had originally proposed to metabotype 300 individuals for the achievement of the first objective. Due to the timing of funding arriving in mid-fall, we missed out on some recruiting time in fall 2023.We recruited throughout spring and into early summer 2024, at which point we decided to proceed with metabotyping. Because of the design--where recruitment of individuals for the controlled diet is dependent on metabotyping results from the first phase--we decided to proceed on the basis that we risked losing interest in the group that was screened in spring 2024 if we did not proceed with the controlled diet study. Ultimately, we are aiming for 15 ODMA non-producers and 15 ODMA producers to enroll in the controlled diet study. The less common metabotype is ODMA non-producers, somewhere between 10-40% of the population according to prior research. An initial pool of 300 would have given us a comfortable margin tohave enough non-producers, but 150 may still be enough,so we are moving ahead to not lose the interest of these 150.We will re-evaluate if we are not able to recruit sufficient non-producers and producers. Our back-up plan indicated in our proposal was to consider proceeding with 10 non-producers and 20 producers. What opportunities for training and professional development has the project provided?The project has involved 3 graduate students and 4undergraduate students in the human subjects research process, including the recruitment, screening and consent of participants, interactions supportingdata collection, and biospecimen processing. Graduate students have also been involved in the design of the diet and protocol for the upcoming feeding study. At present, two graduate student projects are planned for this study, including one food science PhD dissertation project and one dietetics masters capstone research project. How have the results been disseminated to communities of interest?Results are forthcoming. Meanwhile, adescription of the project was published in newsletters for the College of Agriculture and Natural Resources and the MarylandToday newsletter produced by the University's Office of Marketing and Communications in February 2024. Links are provided below: https://agnr.umd.edu/news/who-benefits-flavonoids/ https://today.umd.edu/a-plant-chemical-may-have-big-health-benefits-but-for-who What do you plan to do during the next reporting period to accomplish the goals?We plan to finish HPLC-MS analysis of urine samples already collected in order to complete metabotyping and identify eligible individuals for the dietary intervention study, in support of Objective 1. We will then proceed with delivering the crossover dietary intervention study to 30 individuals, stratified by ODMA producer status,as planned to address Objectives 2 and 3. Alow-catechin control armand an apple-juice containing arm will be used to deliver a controlled dose of catechins.

Impacts
What was accomplished under these goals? In this first period, we have achieved progress toward Objective 1 and 2/3. For Objective 1, we have recruited and conducted a soy eating intervention in 150 individuals. This included completion of electronic screening questionnaires, phone screen interviews, provision of consent, completion of health history questionnaires, background diet data collection, anthropometric measurements, and consumption of a soy snack for 3 consecutive days, followed by provision of a urine sample. Urine samples are currently under analysis to determine metabotype of O-desmethylangolensin (ODMA) producers and non-producers, after which point individuals will be recruited back to participate in the controlled diet study. Objectives 2 and 3 will be completed via a controlled diet study with participants identified in Objective 1. While metabotyping is proceeding, our team has made progress in designing and receiving IRB approval forthe diet study protocol, designing the controlled diet that is low in catechins, securing the apple juice for the catechin intervention, and designing the placebo beverage to match apple juice flavor, color and sugar content.

Publications