Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans

Abstract

Consumption of green tea (GT) and GT polyphenols has prevented a range of cancers in rodents but has had mixed results in humans. Human subjects who drank GT for weeks showed changes in oral microbiome. However, GT-induced changes in RNA in oral epithelium were subject-specific, suggesting GT-induced changes of the oral epithelium occurred but differed across individuals. In contrast, studies in rodents consuming GT polyphenols revealed obvious changes in epithelial gene expression. GT polyphenols are poorly absorbed by digestive tract epithelium. Their metabolism by gut/oral microbial enzymes occurs and can alter absorption and function of these molecules and thus their bioactivity. This might explain the overall lack of consistency in oral epithelium RNA expression changes seen in human subjects who consumed GT. Each human has different gut/oral microbiomes, so they may have different levels of polyphenol-metabolizing bacteria. We speculate the similar gut/oral microbiomes in, for example, mice housed together are responsible for the minimal variance observed in tissue GT responses within a study. The consistency of the tissue response to GT within a rodent study eases the selection of a dose level that affects tumor rates. This leads to the theory that determination of optimal GT doses in a human requires knowledge about the gut/oral microbiome in that human.

The Interplay between Medical Plants and Gut Microbiota in Cancer

“…The catechins act in a dual modality, stimulating healthy gut microbes and inhibiting the proliferation of Campylobacter jejuni, Bacillus cereus, Escherichia coli, Clostridium perfringens, Legionella pneumophila, and Helicobacter pylori through a disruption of the cell membrane. Furthermore, green-tea polyphenols are able to create an overproliferation of Faecalibacterium, Bifidobacterium, Eubacterium, and Roseburia that lead to an increase in SCFAs with proven effects against colorectal cancer because they suppress lipopolysaccharide synthesis and, consequently, potentiate immune system function and exert an anti-inflammatory action [76][77][78][79][80][81][82]. Citrus fruits, like Citrus reticulate, or mandarin oranges; Citrus sinesis, or sweet oranges; Citrus depressa, or flat lemons; Citrus aurantium, or bitter oranges; and, especially, Citrus tangerine, or tangerines, contain nobiletin, a flavone with a chemical structure of three aromatic rings, each one linked to specific molecular groups.…”

“…Experiments in a mouse model about an estrogen-receptor (ER) negative mammary tumor showed that polyphenols alone did not induce a significative change in the gut-microbiota composition of healthy mice, even if they reduced significantly the rate of Firmicutes communities; in contrast, after cancer onset, these natural compounds effectively modified gut microbes, leading to a reduction of Proteobacteria and an increase in Bacterioides, compared to the control group. Furthermore, these changes are more evident after a combined administration of both broccoli sprouts and green-tea polyphenols [76][77][78][79][80][81]. Other plants and vegetables have shown antioxidant and anticancer properties.…”

Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence

“…Green tea contains various types of polyphenols, commonly called green tea polyphenols (GTP), which include flavonoids (catechins), tannins, theaflavins, and phenolic acids [ 23 ]. Major GTPs include catechins (50–55%) like epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC), epigallocatechin-3-gallate (EGCG), and phenolic acids like gallic acids [ 24 ]. GTP undergoes biotransformation and produces various bioactive metabolites including 4′-O-methyl-epigallocatechin (4′-MeEGC); EGCG-sulfate; EGC-sulfate, 5-(3,4′,5′-trihydroxyphenyl)-γ-valerolactone (valeric acid derivatives), and phenolic acids like gallic acid, coumaric acid, and caffeic acid (refer to Table 1 for more details) [ 25 ].…”

“…As aforementioned, catechins are the major ingredients of GTPs, of which EGCG is considered as the major catechin. EGCG possesses an array of biological activities including anti-inflammatory, anti-microbial, antioxidant, anti-platelet aggregation, anti-cancer as well as cardioprotective and neuroprotective properties [ 24 , 26 , 27 ]. Even though GTP (especially EGCG) possesses beneficial properties, its low bioavailability is one of the major issues due to its high water-solubility (unstable), and high sensitivity toward pH, temperature, and light.…”

Green Tea and Its Relation to Human Gut Microbiome

“…Therefore, not only parent compounds (such as EGCG) have been associated with cancer protection but also their metabolites, which raises the question of how the microbial metabolization of polyphenols could affect cancer prevention. This question was raised by Adami et al [ 50 ], claiming that inter-individual variations in the microbial communities could lead to different responses against cancer. If a metabolite is an effective protector, people lacking the species in charge of producing it would potentially have less protection.…”