Systematic Study of Bacterial Carcinogen Metabolism and its Functional Consequences in Chemical Carcinogenesis
EMBARGOED UNTIL 2026-10-19
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Date
2023
Publication Type
Doctoral Thesis
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yes
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EMBARGOED UNTIL 2026-10-19
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Abstract
Exogenous chemicals (‘xenobiotics’) that humans are exposed to can accumulate in our body, interact with our cells in various ways, and potentially result in health problems. The level of accumulation of xenobiotics and the way they accumulate primarily depend on the biochemical modifications of xenobiotics by biological agents such as enzymes (‘biotransformation’) in our body. Different enzymatic reactions can lead to the production of harmful or harmless metabolites, which can subsequently affect how easily the xenobiotics can be eliminated from our body. Previous studies have extensively researched the role of human enzymes in xenobiotic metabolism. However, the role of the human microbiota in metabolizing xenobiotics is less well known. Importantly, it has been shown that there are at least 100-fold more enzymes encoded by an individual’s microbiome compared to the human genome, suggesting that they might also contribute to the metabolic fates of xenobiotics in the human body. Previous studies have shown that gut bacteria contribute to metabolism of synthetic chemicals (e.g. dyes containing azo bonds), clinical drugs (e.g. diltiazem by Bacteroides thetaiotaomicron) and food molecules (e.g. daidzein by Eggerthellaceae strains). However, there is a knowledge gap in how significant such bacterial-mediated metabolism is on a systemic level and how host and bacterial xenobiotic metabolism interact with one another. The primary focus of my PhD is therefore to systematically investigate the metabolism of xenobiotics by bacteria colonizing the human gastrointestinal tract. Particularly, I have selected xenobiotics that are previously known to be potentially carcinogenic and/or mutagenic, which in turn allowed me to investigate the functional consequences of bacteria-mediated xenobiotic biotransformation with respect to cancer development in mouse models. The results of my thesis provide the basis for future research aiming at harnessing the metabolic potential of the microbiota for preventing chemically induced carcinogenesis.
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Examiner: Sturla, Shana J.
Examiner : Zimmermann, Michael
Examiner : Zeller, Georg
Examiner: Aichinger, Georg
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ETH Zurich
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Subject
Toxicology; Metabolism; Gut microbiome
Organisational unit
03853 - Sturla, Shana / Sturla, Shana