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.

Keywords: catechin; gene expression; mucosa; oral squamous cell carcinoma.

Figure 1

Initial products of metabolism of green tea (GT) (-)-epicatechin (EC). Four gut bacteria have enzymes to execute the first C ring cleavage step, while F plautii has been shown to be capable of further metabolism.

Figure 2

Model of shared oral/gut microbiota on ability of GT and GT polyphenols to prevent cancer. represents a bacterium that is efficient at converting GT polyphenols to bioactive forms readily absorbed by digestive tract epithelial cells. The human with high levels of this bacterium would readily process GT catechins to active, absorbed forms, and show a response. The other two humans who lack this bacterium would not.