Influence of human intestinal microbial metabolism on the induction of Nrf2 signaling by green tea catechins as characterized by new approach methodologies (NAMs)

Green tea, which is mainly manufactured from buds and leaves of Camellia sinensis, is one of the most widely consumed beverages around the world. Catechins are the most abundant bioactive constituents in green teas, amounting up to 30% of the total dry weight. (-)-Epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epicatechin (EC) are the four major catechins among others. These catechins are believed to be responsible for various beneficial health effects that have been ascribed to green tea consumption. Though the modes of action underlying these health-promoting effects can be complicated and have not been fully understood, the Kelch-like ECH-associated protein 1/Nuclear factor E2-related factor 2 (Keap1/Nrf2) regulatory network has been reported to play a role. The aim of the present thesis was to obtain better insights into human intestinal microbiota-mediated conversion of model green tea catechins, including the intra- and inter-individual variability, and to characterise the consequences of this conversion for the potential activation of Nrf2-EpRE-mediated gene expression, all using new approach methodologies (NAMs).