Role of drug-metabolizing enzymes in biotransformation of drugs

Yaqoob, Azka; Rehman, Qudsia; Rehman, Kanwal; Akash, Muhammad Sajid Hamid; Hussain, İqbal; Ahmad, Rasheed

doi:10.1016/b978-0-323-95120-3.00013-0

Cited by 3 publications

(2 citation statements)

References 61 publications

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“…The positive control involved exposure of SIHUMIx to Sulfasalazine (CAS 599-79-1), a drug commonly used for irritable bowel disease. This drug relies on bacterial azoreductases to cleave the molecule and release its active components ( Yaqoob et al, 2022 ). The positive control mimicked chemical exposure inoculation, replacing the xenobiotic with sulfasalazine at a final concentration of 1 μM.…”

Section: Methodsmentioning

confidence: 99%

High-throughput screening of the effects of 90 xenobiotics on the simplified human gut microbiota model (SIHUMIx): a metaproteomic and metabolomic study

Castañeda-Monsalve,

Fröhlich,

Haange

et al. 2024

Front. Microbiol.

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The human gut microbiota is a complex microbial community with critical functions for the host, including the transformation of various chemicals. While effects on microorganisms has been evaluated using single-species models, their functional effects within more complex microbial communities remain unclear. In this study, we investigated the response of a simplified human gut microbiota model (SIHUMIx) cultivated in an in vitro bioreactor system in combination with 96 deep-well plates after exposure to 90 different xenobiotics, comprising 54 plant protection products and 36 food additives and dyes, at environmentally relevant concentrations. We employed metaproteomics and metabolomics to evaluate changes in bacterial abundances, the production of Short Chain Fatty Acids (SCFAs), and the regulation of metabolic pathways. Our findings unveiled significant changes induced by 23 out of 54 plant protection products and 28 out of 36 food additives across all three categories assessed. Notable highlights include azoxystrobin, fluroxypyr, and ethoxyquin causing a substantial reduction (log2FC < −0.5) in the concentrations of the primary SCFAs: acetate, butyrate, and propionate. Several food additives had significant effects on the relative abundances of bacterial species; for example, acid orange 7 and saccharin led to a 75% decrease in Clostridium butyricum, with saccharin causing an additional 2.5-fold increase in E. coli compared to the control. Furthermore, both groups exhibited up- and down-regulation of various pathways, including those related to the metabolism of amino acids such as histidine, valine, leucine, and isoleucine, as well as bacterial secretion systems and energy pathways like starch, sucrose, butanoate, and pyruvate metabolism. This research introduces an efficient in vitro technique that enables high-throughput screening of the structure and function of a simplified and well-defined human gut microbiota model against 90 chemicals using metaproteomics and metabolomics. We believe this approach will be instrumental in characterizing chemical-microbiota interactions especially important for regulatory chemical risk assessments.

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Section: Methodsmentioning

confidence: 99%

High-throughput screening of the effects of 90 xenobiotics on the simplified human gut microbiota model (SIHUMIx): a metaproteomic and metabolomic study

Castañeda-Monsalve,

Fröhlich,

Haange

et al. 2024

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…The positive control involved exposure of SIHUMIx to Sulfasalazine (CAS 599-79-1), a drug commonly used for irritable bowel disease. This drug relies on bacterial azoreductases to cleave the molecule and release its active components (Yaqoob et al, 2022). The positive control mimicked chemical exposure inoculation, replacing the xenobiotic with sulfasalazine at a final concentration of 1µM.…”

Section: Determination Of Xenobiotic Concentration and Exposure Of Si...mentioning

confidence: 99%

High-Throughput Screening of the Effects of 90 Xenobiotics on the Simplified Human Gut Microbiota Model (SIHUMIx): A Metaproteomic and Metabolomic Study

Castañeda-Monsalve,

Fröhlich,

Haange

et al. 2023

Preprint

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The human gut microbiota is a complex microbial community with critical functions for the host, including the transformation of various chemicals. While effects on microorganisms has been evaluated using single-species models, their functional effects within more complex microbial communities remain unclear. In this study, we investigated the response of a simplified human gut microbiota model (SIHUMIx) cultivated in an in vitro bioreactor system in combination with 96 deep-well plates after exposure to 90 different xenobiotics, comprising 54 plant protection products and 36 food additives and dyes, at environmentally relevant concentrations. We employed metaproteomics and metabolomics to evaluate changes in bacterial abundances, the production of Short Chain Fatty Acids (SCFAs), and the regulation of metabolic pathways.Our findings unveiled significant changes induced by 23 out of 54 plant protection products and 28 out of 36 food additives across all three categories assessed. Notable highlights include azoxystrobin, fluroxypyr, and ethoxyquin causing a substantial reduction (log2FC <-0.5) in the concentrations of the primary SCFAs: acetate, butyrate, and propionate. Several food additives had significant effects on the relative abundances of bacterial species; for example, acid orange 7 and saccharin led to a 75% decrease inClostridium butyricum, with saccharin causing an additional 2.5-fold increase inE. colicompared to the control. Furthermore, both groups exhibited up- and down-regulation of various pathways, including those related to the metabolism of amino acids such as histidine, valine, leucine, and isoleucine, as well as bacterial secretion systems and energy pathways like starch, sucrose, butanoate, and pyruvate metabolism.This research introduces an efficient in vitro technique that enables high-throughput screening of the structure and function of a simplified and well-defined human gut microbiota model against 90 chemicals using metaproteomics and metabolomics. We believe this approach will be instrumental in characterizing chemical-microbiota interactions especially important for regulatory chemical risk assessments.

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Nutraceuticals in Metabolism and Xenobiotics

Ali

2024

Food Bioactive Ingredients

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Role of drug-metabolizing enzymes in biotransformation of drugs

Cited by 3 publications

References 61 publications

High-throughput screening of the effects of 90 xenobiotics on the simplified human gut microbiota model (SIHUMIx): a metaproteomic and metabolomic study

High-throughput screening of the effects of 90 xenobiotics on the simplified human gut microbiota model (SIHUMIx): a metaproteomic and metabolomic study

High-Throughput Screening of the Effects of 90 Xenobiotics on the Simplified Human Gut Microbiota Model (SIHUMIx): A Metaproteomic and Metabolomic Study

Nutraceuticals in Metabolism and Xenobiotics

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