Degradation of benzo[<i>a</i>]pyrene by bacterial isolates from human skin

Sowada, Juliane; Schmalenberger, Achim; Ebner, Ingo; Luch, Andreas; Tralau, Tewes

doi:10.1111/1574-6941.12276

Cited by 66 publications

(66 citation statements)

References 50 publications

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“…Interestingly, the reactions appeared to involve the formation of hydroxyl metabolites, which, unlike the parent compounds, exhibit estrogenic activities. Additional work has been performed using microorganisms isolated and cultured from human skin (Sowada et al, 2014). Here, the microorganism most commonly identified that was capable of metabolizing benzo[a]pyrene was Micrococcus luteus, and the most likely involved enzyme was identified as a DszA/NtaA-like oxygenase.…”

Section: Impact Of the Gut Microbiome On The Metabolism And Pharmacokmentioning

confidence: 99%

Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry?

Swanson

2015

Drug Metab Dispos

136

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The importance of the gut microbiome in determining not only overall health, but also in the metabolism of drugs and xenobiotics, is rapidly emerging. It is becoming increasingly clear that the gut microbiota can act in concert with the host cells to maintain intestinal homeostasis, cometabolize drugs and xenobiotics, and alter the expression levels of drug-metabolizing enzymes and transporters and the expression and activity levels of nuclear receptors. In this myriad of activities, the impact of the microbiota may be beneficial or detrimental to the host. Given that the interplay between the gut microbiota and host cells is likely subject to high interindividual variability, this work has tremendous implications for our ability to predict accurately a particular drug's pharmacokinetics and a given patient population's response to drugs. In this issue of Drug Metabolism and Disposition, a series of articles is presented that illustrate the progress and challenges that lie ahead as we unravel the intricacies associated with drug and xenobiotic metabolism by the gut microbiota. These articles highlight the underlying mechanisms that are involved and the use of in vivo and in vitro approaches that are currently available for elucidating the role of the gut microbiota in drug and xenobiotic metabolism. These articles also shed light on exciting new avenues of research that may be pursued as we consider the role of the gut microbiota as an endocrine organ, a component of the brain-gut axis, and whether the gut microbiota is an appropriate and amenable target for new drugs.

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Section: Impact Of the Gut Microbiome On The Metabolism And Pharmacokmentioning

confidence: 99%

Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry?

Swanson

2015

Drug Metab Dispos

136

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“…Unless eliminated via conjugation and excretion, the latter is a highly efficient DNA alkylating agent and as such a most potent carcinogen (Luch 2005; Luch and Baird 2010). At the same time, B[ a ]P is a potential substrate for skin bacteria, and although oxidative transformations are likely to occur, we know little about the corresponding metabolites or their toxicological potential for the human host (Sowada et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Toxification of polycyclic aromatic hydrocarbons by commensal bacteria from human skin

et al. 2017

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The ubiquitous occurrence of polycyclic aromatic hydrocarbons (PAHs) leads to constant human exposure at low levels. Toxicologically relevant are especially the high-molecular weight substances due to their (pro-)carcinogenic potential. Following ingestion or uptake, the eukaryotic phase I metabolism often activates these substances to become potent DNA binders, and unsurprisingly metabolism and DNA-adduct formation of model substances such as benzo[a]pyrene (B[a]P) are well studied. However, apart from being subjected to eukaryotic transformations PAHs are also carbon and energy sources for the myriads of commensal microbes inhabiting man’s every surface. Yet, we know little about the microbiome’s PAH-metabolism capacity and its potentially adverse impact on the human host. This study now shows that readily isolable skin commensals transform B[a]P into a range of highly cyto- and genotoxic metabolites that are excreted in toxicologically relevant concentrations during growth. The respective bacterial supernatants contain a mixture of established eukaryotic as well as hitherto unknown prokaryotic metabolites, the combination of which leads to an increased toxicity. Altogether we show that PAH metabolism of the microbiome has to be considered a potential hazard.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-017-1964-3) contains supplementary material, which is available to authorised users.

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“…Gut microbes can metabolize a range of environmental chemicals in ways that can affect their toxicity to the host, including polycyclic aromatic hydrocarbons (PAHs), nitrotoluenes (which are important intermediates in the manufacture of dyes and plastics), and pesticides 67 . PAH degrading microbes have also been observed on human skin 68 . Additionally, gut microbes have also been associated with breakdown and reactivation of a variety of drugs including the cardiovascular drug, digoxin and the cancer drug, irinotecan 69 .…”

Section: Linking Microbiome/metabolome With the Exposomementioning

confidence: 99%

Microbiome and metabolome data integration provides insight into health and disease

Shaffer

Armstrong

Phelan

et al. 2017

Translational Research

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For much of our history, the most basic information about the microbial world has evaded characterization. Next-generation sequencing has led to a rapid increase in understanding of the structure and function of host-associated microbial communities in diverse diseases ranging from obesity to autism. Through experimental systems such as gnotobiotic mice only colonized with known microbes, a causal relationship between microbial communities and disease phenotypes has been supported. Now microbiome research must move beyond correlations and general demonstration of causality to develop mechanistic understandings of microbial influence, including through their metabolic activities. Similar to the microbiome field, advances in technologies for cataloguing small molecules have broadened our understanding of the metabolites that populate our bodies. Integration of microbial and metabolomics data paired with experimental validation has promise for identifying microbial influence on host physiology through production, modification or degradation of bioactive metabolites. Realization of microbial metabolic activities that affect health is hampered by gaps in our understanding of 1) biological properties of microbes and metabolites, 2) which microbial enzymes/pathways produce which metabolites and 3) the effects of metabolites on hosts. Capitalizing upon known mechanistic relationships and filling gaps in our understanding has the potential to enable translational microbiome research across disease contexts.

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Degradation of benzo[a]pyrene by bacterial isolates from human skin

Cited by 66 publications

References 50 publications

Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry?

Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry?

Toxification of polycyclic aromatic hydrocarbons by commensal bacteria from human skin

Microbiome and metabolome data integration provides insight into health and disease

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