The Donor-Dependent and Colon-Region-Dependent Metabolism of (+)-Catechin by Colonic Microbiota in the Simulator of the Human Intestinal Microbial Ecosystem

Abstract

The intestinal absorption of dietary catechins is quite low, resulting in most of them being metabolized by gut microbiota in the colon. It has been hypothesized that microbiota-derived metabolites may be partly responsible for the association between catechin consumption and beneficial cardiometabolic effects. Given the profound differences in gut microbiota composition and microbial load between individuals and across different colon regions, this study examined how microbial (+)-catechin metabolite profiles differ between colon regions and individuals. Batch exploration of the interindividual variability in (+)-catechin microbial metabolism resulted in a stratification based on metabolic efficiency: from the 12 tested donor microbiota, we identified a fast- and a slow-converting microbiota that was subsequently inoculated to SHIME, a dynamic model of the human gut. Monitoring of microbial (+)-catechin metabolites from proximal and distal colon compartments with UHPLC-MS and UPLC-IMS-Q-TOF-MS revealed profound donor-dependent and colon-region-dependent metabolite profiles with 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone being the largest contributor to differences between the fast- and slow-converting microbiota and the distal colon being a more important region for (+)-catechin metabolism than the proximal colon. Our findings may contribute to further understanding the role of the gut microbiota as a determinant of interindividual variation in pharmacokinetics upon (+)-catechin ingestion.

In Vitro Microbial Metabolism of (+)-Catechin Reveals Fast and Slow Converters with Individual-Specific Microbial and Metabolite Markers

“…It has been stated that fecal microbiota from different donors possess different metabolic efficiency of (+)-catechin in our previous research. 34 We estimate the metabolic rate of these donors by calculating the elimination rate constant k after 4 h of incubation based on previously obtained data. 34 On the basis of the obtained k value, it can be concluded that the microbial metabolic rate of (+)-catechin varied greatly among donors, ranging from −0.004 h −1 (donor 9) to 0.200 h −1 (donor 12).…”

“…34 We estimate the metabolic rate of these donors by calculating the elimination rate constant k after 4 h of incubation based on previously obtained data. 34 On the basis of the obtained k value, it can be concluded that the microbial metabolic rate of (+)-catechin varied greatly among donors, ranging from −0.004 h −1 (donor 9) to 0.200 h −1 (donor 12). The variability in metabolic rates leads us to stratify donors 6, 8, 9, and 10 as slow converters to (+)-catechin supplementation, donors 1, 2, 4, and 5 as medium converters, and donors 3, 7, 11, and 12 as fast converters (Table 1).…”

“…It has been stated that fecal microbiota from different donors possess different metabolic efficiency of (+)-catechin in our previous research . We estimate the metabolic rate of these donors by calculating the elimination rate constant k after 4 h of incubation based on previously obtained data .…”

Use of Physiologically Based Kinetic Modeling-Based Reverse Dosimetry to Predict In Vivo Nrf2 Activation by EGCG and Its Colonic Metabolites in Humans

“…For instance, several studies have confirmed that there are substantial interindividual differences in the colonic microbial metabolism of green tea catechins, where potential fast and slow metabolizers may be characterized. 19,64,65 In conclusion, the newly developed PBK model was shown to be able to adequately predict blood concentrations of EGCG and to include the gut microbial metabolism in the model. Although microbial metabolites GA and PG are more capable of inducing Nrf2 pathway activation than EGCG, their contributions to systemic induction of Nrf2-mediated gene expression were predicted to be limited due to their relatively lower systemic concentrations than that of EGCG.…”

Phytonutrients: Sources, bioavailability, interaction with gut microbiota, and their impacts on human health

“…As a member of the flavan-3-ol polyphenol family, catechins are widely distributed in a range of dietary sources, such as tea, cocoa, apple, and kiwi fruit ( 43 , 44 ). Catechins are extremely abundant in polyphenol-rich green tea and its extracts, accounting for approximately one-third of the solids in brewed green tea ( 45 , 46 ).…”