Dataset Information

Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl-γ-Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo-Controlled Human Intervention Trial.

ABSTRACT:

Scope

The majority of ingested flavanols reach the colon where they are catabolized by the microbiota to form hydroxyphenyl-γ-valerolactones (HGVLs). It is not known if the HGVLs are catabolic products of monomeric (epi)catechins (EPC), oligomeric procyanidins (OPCs), or both. Using data from a randomized, double-blind, placebo-controlled crossover trial the relative contributions of catechins and OPC to the bioavailable pool of HGVLs are estimated.

Methods and results

Participants ingested an apple extract once daily for 28 days that delivered the following: i) 70 mg EPC and 65 mg OPC (low dose EPC), ii) 140 mg EPC and 130 mg OPC (high dose EPC), iii) 6 mg EPC and 130 mg OPC (OPC), and iv) a placebo control. Urine is collected over a 24-h period before and after treatments. The median urinary excretion of HGVLs after ingestion of the high dose EPC is tenfold higher than that excreted after ingestion of the OPC that provided an equivalent dose of PC. Approximately 22% of catechins are converted to HGVLs in contrast to PC, for which there is limited conversion.

Conclusion

Monomeric catechins are efficiently converted to derived HGVLs that are absorbed and excreted in human urine, whereas oligomeric PCs are much less efficiently converted.

SUBMITTER: Hollands WJ

PROVIDER: S-EPMC7378946 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl-γ-Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo-Controlled Human Intervention Trial.

Hollands Wendy J WJ Philo Mark M Perez-Moral Natalia N Needs Paul W PW Savva George M GM Kroon Paul A PA

Molecular nutrition & food research 20200420 10

<h4>Scope</h4>The majority of ingested flavanols reach the colon where they are catabolized by the microbiota to form hydroxyphenyl-γ-valerolactones (HGVLs). It is not known if the HGVLs are catabolic products of monomeric (epi)catechins (EPC), oligomeric procyanidins (OPCs), or both. Using data from a randomized, double-blind, placebo-controlled crossover trial the relative contributions of catechins and OPC to the bioavailable pool of HGVLs are estimated.<h4>Methods and results</h4>Participant ...[more]

PMID: 32223044

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Project description:Background: In a recent intervention study, the daily supplementation with 200mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. Methodology/Principal Findings: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 869 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNFα-stimulated endothelial cells. Nuclear factor-kappa B reporter gene assays confirmed that MOF decrease the activity of NF-κB. Strong inter-individual variability in the leukocytes DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. However, in individuals, significant changes in DNA methylation of genes involved in leukocyte rolling, adhesion and cytoskeleton remodelling were seen. At the group level, the variation in DNA methylation related to life style and clinical parameters appeared to overrule the magnitude of effects of supplementation with MOF. Conclusion: Our study revealed that regular consumption of MOF modulates the expression of genes in immune cells which, however, cannot be correlated to alterations in the DNA methylome. Remarkably, at the individual level, genes related to leukocyte adhesion pathways present complex variation in DNA methylation. As such, the individual transcriptional and epigenetic modulation of genes involved in early manifestation of cardiovascular diseases constitutes important subcellular mechanisms by which MOF promote vascular health in humans.

Project description:Background: In a recent intervention study, the daily supplementation with 200mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. Methodology/Principal Findings: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 869 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNFM-NM-1-stimulated endothelial cells. Nuclear factor-kappa B reporter gene assays confirmed that MOF decrease the activity of NF-M-NM-:B. Strong inter-individual variability in the leukocytes DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. However, in individuals, significant changes in DNA methylation of genes involved in leukocyte rolling, adhesion and cytoskeleton remodelling were seen. At the group level, the variation in DNA methylation related to life style and clinical parameters appeared to overrule the magnitude of effects of supplementation with MOF. Conclusion: Our study revealed that regular consumption of MOF modulates the expression of genes in immune cells which, however, cannot be correlated to alterations in the DNA methylome. Remarkably, at the individual level, genes related to leukocyte adhesion pathways present complex variation in DNA methylation. As such, the individual transcriptional and epigenetic modulation of genes involved in early manifestation of cardiovascular diseases constitutes important subcellular mechanisms by which MOF promote vascular health in humans. Two-colors experiment, 7 volunteers : blood samples of 7 men, before and after an intervention of 8 weeks with daily intake of MOF (14 samples).

Project description:BackgroundCardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded.MethodsIn a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets.ResultsIn the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P ≤ 0.05).ConclusionOur integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans.Trial registrationClinicalTrials.gov NCT00742287.

Dataset Information

Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl-γ-Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo-Controlled Human Intervention Trial.

Scope

Methods and results

Conclusion

Publications

Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl-γ-Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo-Controlled Human Intervention Trial.

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