Interindividual Differences in Human In Vitro Intestinal Microbial Conversion of Green Tea (‐)‐Epigallocatechin‐3‐<i>O</i>‐Gallate and Consequences for Activation of Nrf2 Mediated Gene Expression

Liu, Chen; Vervoort, Jacques; Elzen, Joris van den; Beekmann, Karsten; Baccaro, Marta; Haan, Laura de; Rietjens, Ivonne M.C.M.

doi:10.1002/mnfr.202000934

Cited by 13 publications

(34 citation statements)

References 52 publications

(68 reference statements)

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“…Donor 1 and Donor 2 with personal availability and without medication history were enrolled for the subsequent SHIME run. Previous studies established the correlation of different microbial compositions with metabolites of catechins [ 18 , 19 ]. Thus, the microbial profiles of the fecal inoculum of these two selected donors were analyzed as shown in Supplementary Materials Figure S1 .…”

Section: Resultsmentioning

confidence: 99%

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

Herreweghen

Mey

et al. 2021

Molecules

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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.

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Section: Resultsmentioning

confidence: 99%

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

Herreweghen

Mey

et al. 2021

Molecules

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“…The activity of EC and 3,4-diHPV in inducing Nrf2 gene transcription was determined using the U2OS Nrf2 CALUX reporter gene assay. The method was performed essentially as previously described ( 22 ). Briefly, U2OS Nrf2 CALUX cells were cultured in a black 96-well microplate with a clear bottom (Greiner Bio-One) at a density of 2 × 10 5 cells/ml (2 × 10 4 cells in 100 μL culture medium per well) for 24 h to let the cells attach to the bottom.…”

Section: Methodsmentioning

confidence: 99%

“…As is well-known, colonic microbiota play a critical role in the degradation of EC and the formation of 3,4-diHPV. It has been widely accepted that due to the different age, gender, ethnic factors, and diverse lifestyle, the inter-individual microbial compositions could vary substantially ( 21 ), hence, affecting the metabolic profiles ( 20 , 22 ). On the other hand, the microbiota composition is considered to be relatively stable within healthy individuals ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Intra- and Inter-individual Differences in the Human Intestinal Microbial Conversion of (-)-Epicatechin and Bioactivity of Its Major Colonic Metabolite 5-(3′,4′-Dihydroxy-Phenyl)-γ-Valerolactone in Regulating Nrf2-Mediated Gene Expression

2022

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(-)-Epicatechin (EC) is one of the most popular polyphenols present in various food products in daily life. Upon intake, it is intensively metabolized by microbiota in the large intestine. In the present study, intra- and inter-individual variations in this gut microbial conversion of EC and the concomitant formation of its major metabolites, including 5-(3′,4′-dihydroxy phenyl)-γ-valerolactone (3,4-diHPV), were identified and quantified via liquid chromatography triple quadrupole mass spectrometry (LC-TQ-MS) in anaerobic fecal incubations. In addition, the bioactivity of EC and 3,4-diHPV in activating Nrf2-mediated gene expression was tested quantifying their effects in the U2OS Nrf2 CALUX assay (a reporter gene assay that is used to test the potency of chemicals in activation of Nrf2 signaling), and on the expression levels of Nrf2-related proteins in Hepa1c1c7 and Caco-2 cells via nanoLC-MSMS. A quantitative real-time polymerase chain reaction (RT-qPCR) was carried out to confirm selected Nrf2-regulated gene expressions at the mRNA level. Results obtained show that both intra- and inter-individual differences exist in human gut microbial EC degradation and 3,4-diHPV formation, with inter-individual differences being more distinct than intra-individual differences. The metabolite, 3,4-diHPV, showed higher potency in the U2OS Nrf2 CALUX assay than EC itself. Among the obviously altered Nrf2-related proteins, 14 and 10 Nrf2-associated proteins were upregulated to a higher extent upon 3,4-diHPV treatment than in the EC treated group for Hepa1c1c7 and Caco-2 cells, respectively. While only three and four of these Nrf2-associated proteins were induced at a higher level upon EC than upon 3,4-diHPV treatment for Hepa1c1c7 and Caco-2 cells, respectively. RT-qPCR results showed that indeed Nrf2-mediated genes (e.g., Nqo1 and Ugt1a) were only induced significantly in 3,4-diHPV treated and not in EC treated Hepa1c1c7 cells. Taken together, the results suggest that the major colonic EC metabolite, 3,4-diHPV, was more capable of inducing Nrf2-mediated gene expression than its parent compound EC. This implies that the evident inter- and intra-individual differences in the microbial conversion of EC to this major metabolite 3,4-diHPV may affect the overall health-promoting effects of EC consumption related to the Nrf2 pathway activation.

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“…Moreover, the inter individual differences in intestinal microbial metabolism was found to affect not only (-)-epigallocatechin-3-O-gallate metabolism but rather its health effects (92) .…”

Section: Occurrence and Metabolismmentioning

confidence: 99%

“…Another in vitro study was developed to characterize inter individual differences in gut microbial metabolism of (-)-epigallocatechin-3-O-gallate by using anaerobic human faecal incubations. The major metabolites were identified as gallic acid, pyrogallol, phenylpropane-2-ols, phenyl-γ-valerolactones, and 5-(3′,5′- Accepted manuscript dihydroxyphenyl)valeric acid with substantial inter individual variations (92) .…”

Section: Occurrence and Metabolismmentioning

confidence: 99%

Interactions between dietary flavonoids and the gut microbiome: a comprehensive review

et al. 2021

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Flavonoids are natural polyphenol secondary metabolites that are widely produced in planta. Flavonoids are ubiquities in human dietary intake and exhibit a myriad of health benefits. Flavonoids-induced biological activities are strongly influenced by their in-situ availability in the human GI tract, as well as the levels of which are modulated by interaction with the gut bacteria. As such, assessing flavonoids-microbiome interactions is considered a key to understand their physiological activities. Here, we review the interaction between the various classes of dietary flavonoids (flavonols, flavones, flavanones, isoflavones, flavan-3-ols, and anthocyanins) and gut microbiota. We aim to provide a holistic overview of the nature and identity of flavonoids on diet, and highlight how flavonoids chemical structure, metabolism, and impact on humans and their microbiomes are interconnected. Emphasis is placed on how flavonoids and their biotransformation products affect gut microbiota population, influence gut homeostasis, and induce measurable physiological changes and biological benefits.

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Interindividual Differences in Human In Vitro Intestinal Microbial Conversion of Green Tea (‐)‐Epigallocatechin‐3‐O‐Gallate and Consequences for Activation of Nrf2 Mediated Gene Expression

Cited by 13 publications

References 52 publications

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

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

Intra- and Inter-individual Differences in the Human Intestinal Microbial Conversion of (-)-Epicatechin and Bioactivity of Its Major Colonic Metabolite 5-(3′,4′-Dihydroxy-Phenyl)-γ-Valerolactone in Regulating Nrf2-Mediated Gene Expression

Interactions between dietary flavonoids and the gut microbiome: a comprehensive review

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