Interindividual Differences in Human Intestinal Microbial Conversion of (−)-Epicatechin to Bioactive Phenolic Compounds

Abstract

To quantify interindividual differences in the human intestinal microbial metabolism of (−)-epicatechin (EC), in vitro anaerobic incubations with fecal inocula from 24 healthy donors were conducted. EC-derived colonic microbial metabolites were qualitatively and quantitively analyzed by liquid chromatography triple quadrupole mass spectrometry (LC-TQ-MS) and liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS). Quantitative microbiota characterization was achieved by 16S rRNA analysis. The results obtained show 1-(3′,4′-dihydroxyphenyl)-3-(2″,4″,6″-dihydroxyphenyl)-2-propanol (3,4-diHPP-2-ol) and 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (3,4-diHPV) to be key intermediate microbial metabolites of EC and also revealed the substantial interindividual differences in both the rate of EC conversion and the time-dependent EC metabolite pattern. Furthermore, substantial differences in microbiota composition among different individuals were detected. Correlations between specific microbial phylotypes and formation of certain metabolites were established. It is concluded that interindividual differences in the intestinal microbial metabolism of EC may contribute to interindividual differences in potential health effects of EC-abundant dietary foods or drinks.

Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry

“…Metabolism to succinate and propionate has been associated with improved glucose homeostasis. [ 59 , 60 ] Lachnospiraceae NC2004 [ 61 ], a genus associated with ring cleavage of polyphenolic compounds found in high-fiber foods, was also enriched after FS. Additionally, within EA, Victivallus , a cellobiose degrading bacteria, and Ruminiclostridia , a lignocellulose-degrading bacteria, were enriched after FS and may reflect higher dietary fiber, whole grains, and vegetable intake by EA in our study ( Table 1 ).…”

Main drivers of (poly)phenol effects on human health: metabolite production and/or gut microbiota-associated metabotypes?

“…This issue is even more relevant when tentative "metabotypes" have been proposed after the analysis of in vitro or in vivo samples from a few volunteers (n1015), which is, unfortunately, the most common scenario in those studies that recurrently use the term "metabotype" in the context of (poly)phenols metabolism. 117,[128][129][130] Indeed, after analysing such small sample sizes, high and low producers could be tentatively identified by specifying an arbitrary limit to establish such a classification. However, in a large cohort, it could be possible that after applying the same cut-off, these same volunteers could be all grouped within the high producers or all of them within the low producers.…”

Protein Adducts and Protein Oxidation as Molecular Mechanisms of Flavonoid Bioactivity

“…Many studies have demonstrated that flavonoids are extensively metabolized after absorption in the intestine (reviewed in [ 77 ]). It is also firmly established that gut microbes degrade flavonoids into a variety of metabolic products that are absorbed into the blood stream and eventually excreted [ 15 , 16 ]. These products include sulfated and glucuronidated flavonoids from enzymes in human enterocytes as well as a variety of microbial products with hydroxylated phenyl groups.…”

“…These metabolic products will have different physical and chemical properties from their flavonoid parents, but it is possible that, in some cases, they could still be oxidized to electrophilic quinones. For example, the major microbial flavonoid degradation product 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (3,4-diHPV) [ 15 ] still possesses a catechol group and therefore seems likely to be readily oxidized to a quinone. Because of the metabolic transformations that occur after passage of absorbed flavonoid from intestinal epithelium into the circulatory system, it seems probable that most of the flavonoid bioactivity will occur in these intestinal cells rather than in other tissues since the bulk of absorbed flavonoid metabolites are eventually excreted [ 16 ].…”

“…Unfortunately, papers are still being published that report the isolation of phenolic metabolites from various plant sources and use a rationale of antioxidant activity based on radical-scavenging assays as a justification for some proposed health benefit. However, the concentration of flavonoids and their colonic metabolites in human plasma is around five-fold less than the concentration of endogenous radical-scavenging metabolites such as α-tocopherol or ascorbic acid [ 15 , 16 , 17 ]. The majority of consumed dietary flavonoids are absorbed from the small intestine as degradative metabolites after being metabolized by gut microbes [ 16 , 18 ], which strongly supports the conclusion that dietary flavonoids simply will not accumulate in most human tissue at sufficient concentrations for their radical scavenging activity to be relevant.…”