Intestinal-level anti-inflammatory bioactivities of catechin-rich green tea: Rationale, design, and methods of a double-blind, randomized, placebo-controlled crossover trial in metabolic syndrome and healthy adults

Abstract

Metabolic endotoxemia initiates low-grade chronic inflammation in metabolic syndrome (MetS) and provokes the progression towards more advanced cardiometabolic disorders. Our recent works in obese rodent models demonstrate that catechin-rich green tea extract (GTE) improves gut barrier integrity to alleviate the translocation of gut-derived endotoxin and its consequent pro-inflammatory responses mediated through Toll-like receptor-4/nuclear factor κB (TLR4/NFκB) signaling. The objective of this clinical trial is to establish the efficacy of GTE to alleviate metabolic endotoxemia-associated inflammation in persons with MetS by improving gut barrier function. We plan a double-blind, placebo-controlled cross-over trial in persons with MetS and age- and gender-matched healthy persons (18–65 y; n = 20/group) who will receive a low-energy GTE-rich (1 g/day; 890 mg total catechins) confection snack food while following a low-polyphenol diet for 28 days. Assessments will include measures of circulating endotoxin (primary outcome) and secondary outcomes including biomarkers of endotoxin exposure, region-specific measures of intestinal permeability, gut microbiota composition, diversity, and functions, intestinal and systemic inflammatory responses, and catechins and microbiota-derived catechin metabolites. Study outcomes will provide the first report of the GTE-mediated benefits that alleviate gut barrier dysfunction in relation to endotoxemia-associated inflammation in MetS persons. This is expected to help establish an effective dietary strategy to mitigate the growing burden of MetS that currently affects ~35% of Americans.

Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome

“…Immediately after the SESI-HRMS analysis of ampicillin treatment, 1 mL of microbial cultures was placed into 2 mL tubes and kept at −80 °C until further metabolite extraction. The previously published method was modified for the analysis of C2–C7 volatile fatty acids from the liquid cultures [ 53 ]. Briefly, the collected supernatant was centrifuged at 14,000 rpm for 10 min.…”

Tea Bioactive Modulate Innate Immunity: In Perception to COVID-19 Pandemic

“…Another important aspect is "gut-lung" crosstalk, in recent times this phenomenon has gained lot of attention and it is widely recognized that an ideal gut microenvironment is essential for a balanced immune response not only for gastrointestinal track but also for maintaining respiratory homeostasis (41). Experimental and clinical evidences have indicated that host stress response activates macrophages and neutrophils in alveolar cells, leading to increase in pro-inflammatory cytokines and catecholamines (42). This signal is strongly correlated with growth and virulence of bacterial community like streptococcus pneumonia, klebsiella pneumonia perpetuating alveolar inflammation (42).…”

“…Experimental and clinical evidences have indicated that host stress response activates macrophages and neutrophils in alveolar cells, leading to increase in pro-inflammatory cytokines and catecholamines (42). This signal is strongly correlated with growth and virulence of bacterial community like streptococcus pneumonia, klebsiella pneumonia perpetuating alveolar inflammation (42). This change in the inflamed lungs also leads to "gut dysbiosis" altering gut microbiota.…”

“…This may explain severity of gastrointestinal problem, e.g., diarrhea in COVID 19 patients (41). The "gut-lung" axis is a bidirectional phenomenon, which can explain that an altered bacterial diversity in gut also can trigger a cascade of inflammatory signals in the lungs through butyrate, propionate and secondary bile acids secreted by bacteroides which can bind to receptors of dendritic cells and macrophages (41,42). Murine and clinical intervention studies indicated that tea catechins have prebiotic activities which help in improving gut barrier integrity, decrease LPS containing gram negative bacterial community in Subject followed overnight fasting before taking 500 ml of green tea.…”

“…Blood sample was collected before the intervention and at 30, 60, 90, 120, 180, 240, and 360 min after the ingestion. The European Food Safety Agency (EFSA) based on clinical trial has recommended intake of EGCG/day to less than 800 mg. the gut, and regulate intestinal tight junction protein expressions (42). Tea also contain alkaloids methylxanthine, namely, caffeine (CAF) and its intermediates, theophylline (TPI), and theobromine (TBR) (43).…”