The human colonic microflora influences the alterations of xenobiotic-metabolizing enzymes by catechins in male F344 rats

Lhoste, Évelyne; Ouriet, V; Bruel, Sandrine; Flinois, Jean‐Pierre; Brézillon, Christophe; Magdalou, Jacques; Chèze, Catherine; Nugon-Baudon, Lionelle

doi:10.1016/s0278-6915(03)00010-3

Cited by 45 publications

(27 citation statements)

References 39 publications

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“…Such humanized (gnotobiotic) mice provide a model system for controlling host genotype, gut microbiota composition, diet, and housing conditions. Demonstrating the applicability of the model, several studies involving germ-free and humanized rodents showed that the presence and, therefore, bioavailability of certain polyphenol derivatives depended on the presence of an intestinal microbiota (48)(49)(50). So far, no studies have followed the composition of the intestinal microbiota in humanized rodents fed a polyphenol-rich diet.…”

Section: Humanized Mice Modelsmentioning

confidence: 99%

Metabolic fate of polyphenols in the human superorganism

Duynhoven

Vaughan

Jacobs

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

471

330

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Dietary polyphenols are components of many foods such as tea, fruit, and vegetables and are associated with several beneficial health effects although, so far, largely based on epidemiological studies. The intact forms of complex dietary polyphenols have limited bioavailability, with low circulating levels in plasma. A major part of the polyphenols persists in the colon, where the resident microbiota produce metabolites that can undergo further metabolism upon entering systemic circulation. Unraveling the complex metabolic fate of polyphenols in this human superorganism requires joint deployment of in vitro and humanized mouse models and human intervention trials. Within these systems, the variation in diversity and functionality of the colonic microbiota can increasingly be captured by rapidly developing microbiomics and metabolomics technologies. Furthermore, metabolomics is coming to grips with the large biological variation superimposed on relatively subtle effects of dietary interventions. In particular when metabolomics is deployed in conjunction with a longitudinal study design, quantitative nutrikinetic signatures can be obtained. These signatures can be used to define nutritional phenotypes with different kinetic characteristics for the bioconversion capacity for polyphenols. Bottom-up as well as top-down approaches need to be pursued to link gut microbial diversity to functionality in nutritional phenotypes and, ultimately, to bioactivity of polyphenols. This approach will pave the way for personalization of nutrition based on gut microbial functionality of individuals or populations.polyphenol bioconversion | gut microbiota | metabolomics | metagenomics | microbiomics

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Section: Humanized Mice Modelsmentioning

confidence: 99%

Metabolic fate of polyphenols in the human superorganism

Duynhoven

Vaughan

Jacobs

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

471

330

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“…Indirect potentiating/lowering effect on drug metabolism depending on the type of co-administered drug, the metabolic pathway adapted, and the effect of the resulting metabolite [32] 2-methoxy esterone Anti-angiogenic Members of the gut microbiota are believed to convert 2-methoxy esterone to the active steroid form. This was demonstrated upon incubation of 2-methoxy esterone with isolated rat cecum, where two different reactions were found to take place: oxidoreduction at C17 and demethylation at C2 resulting into the active form.…”

Section: Carcinogenic Agentsmentioning

confidence: 99%

Diet-Microbiota Interactions and their Implications for Healthy Living

2014

Health and the Gut

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The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

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“…Inoculation of germ-free rodents with a human faecal microbiota, human-microbiota associated (HMA) animals, effectively mimics human microbial metabolism and thus provides a reliable model to study the human gut microbial ecosystem as well as metabolism (Hirayama & Itoh, 2005;Turnbaugh & Gordon, 2009). Some HMA rodent studies on catechin and isoflavone metabolism have been performed, but without investigating the effects on composition and activity of the microbial community itself (Bowey et al, 2003;Lhoste et al, 2003). Germ-free rodents inoculated with specific bacterial strains have been used to study polyphenol conversion, but appear to be of limited added value for studying microbial conversions as they have so far just confirmed in vitro results (Blaut et al, 2003;Possemiers et al, 2008).…”

Section: Models Facilitate Mechanistic Studiesmentioning

confidence: 99%

Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities

et al. 2010

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Polyphenols, ubiquitously present in the food we consume, may modify the gut microbial composition and/or activity, and moreover, may be converted by the colonic microbiota to bioactive compounds that influence host health. The polyphenol content of fruit and vegetables and derived products is implicated in some of the health benefits bestowed on eating fruit and vegetables. Elucidating the mechanisms behind polyphenol metabolism is an important step in understanding their health effects. Yet, this is no trivial assignment due to the diversity encountered in both polyphenols and the gut microbial composition, which is further confounded by the interactions with the host. Only a limited number of studies have investigated the impact of dietary polyphenols on the complex human gut microbiota and these were mainly focused on single polyphenol molecules and selected bacterial populations. Our knowledge of gut microbial genes and pathways for polyphenol bioconversion and interactions is poor. Application of specific in vitro or in vivo models mimicking the human gut environment is required to analyse these diverse interactions. A particular benefit can now be gained from next-generation analytical tools such as metagenomics and metatranscriptomics allowing a wider, more holistic approach to the analysis of polyphenol metabolism. Understanding the polyphenol–gut microbiota interactions and gut microbial bioconversion capacity will facilitate studies on bioavailability of polyphenols in the host, provide more insight into the health effects of polyphenols and potentially open avenues for modulation of polyphenol bioactivity for host health.

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The human colonic microflora influences the alterations of xenobiotic-metabolizing enzymes by catechins in male F344 rats

Cited by 45 publications

References 39 publications

Metabolic fate of polyphenols in the human superorganism

Metabolic fate of polyphenols in the human superorganism

Diet-Microbiota Interactions and their Implications for Healthy Living

Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities

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