Dietary Green Tea Confection For Resolving Gut Permeability-Induced Metabolic Endotoxemia In Obese Adults

Ohio State University40 enrolled

Overview

This study is focused on assessing gastrointestinal-level improvements by which green tea limits metabolic endotoxemia. It is completed in two phases. Phase I consists of a pharmacokinetic study to examine the bioavailability of green tea catechins among lean and obese persons who consumed a single dose of a green tea extract (GTE)-containing confection. These persons will then complete phase 2, which consists of a parallel design randomized controlled in which lean and obese persons will consume placebo or GTE confections. It is expected that catechin-rich green tea will improve gut barrier function to prevent endotoxin translocation and associated low-grade inflammation. Outcomes will therefore support dietary recommendations for green tea to alleviate obesity-related inflammatory responses. Specifically, the study is expected to demonstrate that a green tea confection snack food can attenuate metabolic endotoxemia in association with restoring gastrointestinal health.

Obesity is a major public health concern in the United States, with over two-thirds of the adult population classified as overweight or obese. Obesity is characterized by low-grade chronic inflammation that, in part, is mediated by metabolic endotoxemia. Metabolic endotoxemia describes increased circulating levels of gut-derived endotoxin (a bacterial product derived from Gram-negative bacteria in the intestines) that results from gut barrier dysfunction, a phenomenon that is common in obesity. Studies in rodents models have shown that dietary supplementation with green tea extract (GTE) reduces metabolic endotoxemia in association with improved gut health. This clinical trial will therefore investigate the extent to which a green tea confection snack food can alleviate metabolic endotoxemia and restore gut health in obese humans. It is hypothesized that 4-week daily ingestion of a green tea extract (GTE)-rich confection will limit metabolic endotoxemia by decreasing gut barrier permeability. This study will address the following objectives: 1) define alterations in catechin pharmacokinetics in obese compared with healthy adults, 2) demonstrate improvements in gut barrier function by GTE, and 3) demonstrate GTE-mediated amelioration of microbial dysbiosis. To test the hypothesis, all participants will initially complete a 12-h pharmacokinetics study to define the influence of obesity on catechin bioavailability and metabolism. They will then be randomized to complete a double-blind, randomized, placebo-controlled trial where they will receive a GTE-rich or placebo confection for 4 weeks. Prior to and upon completing the intervention, participants will undergo a gut permeability test, fecal samples will be collected for microbiota composition analysis, and blood samples will be collected to assess endotoxin and inflammatory biomarkers. Upon successfully completing this study, it is anticipated that chronic consumption of a green tea confection will be demonstrated to be an effective dietary strategy to reduce metabolic endotoxemia and improve gut health.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Overweight/obese (BMI = 28-40 kg/m2) * Fasting glucose \< 126 mg/dL * Normotensive (blood pressure \< 140/90 mmHg) * Non-dietary supplement user * Non-smoker Exclusion Criteria: * Regular tea drinkers (\> 2 cups/week) * Vegetarians * Use of medications to manage diabetes, hypertension, or hyperlipidemia * Use of any medications known to be contraindicated for use with green tea ingestion * User of dietary supplements, prebiotics, or probiotics * Recent use of antibiotics or anti-inflammatory agents * Women who are pregnant or lactating or have initiated or changed birth control in the past 3-months * Individuals with gastrointestinal disorders or surgeries * Individuals with hemochromatosis * Alcohol intake \> 3 drinks per day * Any history of cancer

Outcomes

Primary Outcomes

Endotoxin

Serum endotoxin concentration

Time frame: Week 0 - Fasting

Endotoxin

Serum endotoxin concentration

Time frame: Week 2 - Fasting

Endotoxin

Serum endotoxin concentration

Time frame: Week 4 - Fasting

Secondary Outcomes

Gut Permeability - Lactulose to Mannitol Ratio

Urinary Lactulose/Mannitol Ratio (mg/mg)

Time frame: Week 0 - 0-5 hours

Gut Permeability - Lactulose to Mannitol Ratio

Urinary Lactulose/Mannitol Ratio (mg/mg)

Time frame: Week 0 - 6-24 hours

Gut Permeability - Lactulose to Mannitol Ratio

Urinary Lactulose/Mannitol Ratio (mg/mg)

Time frame: Week 4 - 0-5 hours

Gut Permeability - Lactulose to Mannitol Ratio

Urinary Lactulose/Mannitol Ratio (mg/mg)

Time frame: Week 4 - 6-24 hours

Gut Permeability - Sucralose to Erythritol Ratio

Urinary Sucralose/Erythritol Ratio (mg/mg)

Time frame: Week 0 - 6-24 hours

Gut Permeability - Sucralose to Erythritol Ratio

Urinary Sucralose/Erythritol Ratio (mg/mg)

Time frame: Week 0 - 0-24 hours

Urinary Sucralose/Erythritol Ratio (mg/mg)

Ratio of excretion of urinary sugars (Sucralose to Erythritol)

Time frame: Week 4 - 6-24 hours

Gut Permeability - Sucralose to Erythritol Ratio

Urinary Sucralose/Erythritol Ratio (mg/mg)

Time frame: Week 4 - 0-24 hours

Firmicutes to Bacteroidetes Ratio - Microbiota

Ratio of fecal relative Firmicutes (% abundance)/Bacteroidetes (% abundance)

Time frame: Week 0

Firmicutes to Bacteroidetes Ratio - Microbiota

Ratio of fecal relative Firmicutes (% abundance)/Bacteroidetes (% abundance)

Time frame: Week 4

Bioavailability - Epigallocatechin Gallate

Area under the curve (AUC) of plasma epigallocatechin calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epigallocatechin gallate is measured in umol/L over time (hours) resulting in the AUC.

Time frame: Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection

Bioavailability - Epigallocatechin

Area under the curve (AUC) of plasma epigallocatechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epigallocatechin is measured in umol/L over time (hours) resulting in the AUC.

Time frame: Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection

Bioavailability - Epicatechin Gallate

Area under the curve (AUC) of plasma epicatechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epicatechins is measured in umol/L over time (hours) resulting in the AUC.

Time frame: Prior to the intervention enrollment...0-12 hours post-ingestion of a green tea confection

Bioavailability - Epicatechin

Area under the curve (AUC) of plasma epicatechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection. Epicatechin is measured in umol/L over time (hours) resulting in the AUC.

Time frame: Prior to intervention enrollment...0-12 hours post-ingestion of a green tea confection

Cmax of Epigallocatechin Gallate

Maximum plasma concentration of catechins calculated from blood collected at 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12 hours post-ingestion of green tea confection