Dataset Information

Bioaccumulation of therapeutic drugs by human gut bacteria: duloxetine accumulation at different concentrations (L.saccharolytica;E.coli assays)

ABSTRACT:

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of 15 structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before.

Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine.

Taken together, bioaccumulation by gut bacteria might be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner.

Linked studies;

UPLC-MS/MS assays of Bifidobacterium animalis subsp. lactis are reported in MTBLS1264.

UPLC-MS/MS assays of Escherichia coli ED1a, Clostridium saccharolyticum, Escherichia coli IAI1, Streptococcus salivarius, Eubacterium rectale, Lactobacillus plantarum WCFS1 and Lactococcus lactis subsp. lactis Il1403 are reported in MTBLS1627.

UPLC-MS/MS assay of Bacteroides uniformis and Clostridium saccharolyticum is reported in MTBLS1757.

UPLC-MS/MS assay of Clostridium saccharolyticum, Escherichia coli ED1a, Escherichia coli IAI1, Lactobacillus plantarum WCFS1, Lactococcus lactis subsp. lactis Il1403 and Streptococcus salivarius is reported in MTBLS1791.

UPLC-MS/MS assay of Eubacterium rectale and Streptococcus salivarius is reported in MTBLS1792.

UPLC-MS/MS assay of Lacrimispora saccharolytica and standards is reported in MTBLS2885.

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Prasad Phapale Sergej Andrejev Sonja Blasche Kiran Patil

PROVIDER: MTBLS1319 | MetaboLights | 2021-07-20

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS1319	Other
	FILES	Other
	a_MTBLS1319_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS1319_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Publications

Bioaccumulation of therapeutic drugs by human gut bacteria.

Klünemann Martina M Andrejev Sergej S Blasche Sonja S Mateus Andre A Phapale Prasad P Devendran Saravanan S Vappiani Johanna J Simon Bernd B Scott Timothy A TA Kafkia Eleni E Konstantinidis Dimitrios D Zirngibl Katharina K Mastrorilli Eleonora E Banzhaf Manuel M Mackmull Marie-Therese MT Hövelmann Felix F Nesme Leo L Brochado Ana Rita AR Maier Lisa L Bock Thomas T Periwal Vinita V Kumar Manjeet M Kim Yongkyu Y Tramontano Melanie M Schultz Carsten C Beck Martin M Hennig Janosch J Zimmermann Michael M Sévin Daniel C DC Cabreiro Filipe F Savitski Mikhail M MM Bork Peer P Typas Athanasios A Patil Kiran R KR

Nature 20210908 7877

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently1 and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had n ...[more]

PMID: 34497420

Similar Datasets

Project description:Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of 15 structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before.Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine.Taken together, bioaccumulation by gut bacteria might be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner. Linked studies;UPLC-MS/MS assays of Bifidobacterium animalis subsp. lactis are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1264' rel='noopener noreferrer' target='_blank'>MTBLS1264</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and Escherichia coli IAI1 is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1319' rel='noopener noreferrer' target='_blank'>MTBLS1319</a>.UPLC-MS/MS assays of Escherichia coli ED1a, Clostridium saccharolyticum, Escherichia coli IAI1, Streptococcus salivarius, Eubacterium rectale, Lactobacillus plantarum WCFS1 and Lactococcus lactis subsp. lactis Il1403 are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1627' rel='noopener noreferrer' target='_blank'>MTBLS1627</a>.UPLC-MS/MS assay of Clostridium saccharolyticum, Escherichia coli ED1a, Escherichia coli IAI1, Lactobacillus plantarum WCFS1, Lactococcus lactis subsp. lactis Il1403 and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1791' rel='noopener noreferrer' target='_blank'>MTBLS1791</a>.UPLC-MS/MS assay of Eubacterium rectale and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1792' rel='noopener noreferrer' target='_blank'>MTBLS1792</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and standards is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS2885' rel='noopener noreferrer' target='_blank'>MTBLS2885</a>.

Project description:Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before. Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug intracellularly without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine. Taken together, bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner. Linked studies:UPLC-MS/MS assays of Bifidobacterium animalis subsp. lactis are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1264' rel='noopener noreferrer' target='_blank'>MTBLS1264</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and Escherichia coli IAI1 is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1319' rel='noopener noreferrer' target='_blank'>MTBLS1319</a>.UPLC-MS/MS assays of Escherichia coli ED1a, Clostridium saccharolyticum, Escherichia coli IAI1, Streptococcus salivarius, Eubacterium rectale, Lactobacillus plantarum WCFS1 and Lactococcus lactis subsp. lactis Il1403 are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1627' rel='noopener noreferrer' target='_blank'>MTBLS1627</a>.UPLC-MS/MS assay of Bacteroides uniformis and Clostridium saccharolyticum is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1757' rel='noopener noreferrer' target='_blank'>MTBLS1757</a>.UPLC-MS/MS assay of Clostridium saccharolyticum, Escherichia coli ED1a, Escherichia coli IAI1, Lactobacillus plantarum WCFS1, Lactococcus lactis subsp. lactis Il1403 and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1791' rel='noopener noreferrer' target='_blank'>MTBLS1791</a>.UPLC-MS/MS assay of Eubacterium rectale and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1792' rel='noopener noreferrer' target='_blank'>MTBLS1792</a>.

Project description:Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of 15 structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before.Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine.Taken together, bioaccumulation by gut bacteria might be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner. Linked studies;UPLC-MS/MS assays of Bifidobacterium animalis subsp. lactis are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1264' rel='noopener noreferrer' target='_blank'>MTBLS1264</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and Escherichia coli IAI1 is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1319' rel='noopener noreferrer' target='_blank'>MTBLS1319</a>.UPLC-MS/MS assays of Escherichia coli ED1a, Clostridium saccharolyticum, Escherichia coli IAI1, Streptococcus salivarius, Eubacterium rectale, Lactobacillus plantarum WCFS1 and Lactococcus lactis subsp. lactis Il1403 are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1627' rel='noopener noreferrer' target='_blank'>MTBLS1627</a>.UPLC-MS/MS assay of Bacteroides uniformis and Clostridium saccharolyticum is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1757' rel='noopener noreferrer' target='_blank'>MTBLS1757</a>.UPLC-MS/MS assay of Clostridium saccharolyticum, Escherichia coli ED1a, Escherichia coli IAI1, Lactobacillus plantarum WCFS1, Lactococcus lactis subsp. lactis Il1403 and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1791' rel='noopener noreferrer' target='_blank'>MTBLS1791</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and standards is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS2885' rel='noopener noreferrer' target='_blank'>MTBLS2885</a>.

Project description:Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before. Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug intracellularly without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine. Taken together, bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner. Linked studies;UPLC-MS/MS assay of Lacrimispora saccharolytica and Escherichia coli IAI1 is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1319' rel='noopener noreferrer' target='_blank'>MTBLS1319</a>.UPLC-MS/MS assays of Escherichia coli ED1a, Clostridium saccharolyticum, Escherichia coli IAI1, Streptococcus salivarius, Eubacterium rectale, Lactobacillus plantarum WCFS1 and Lactococcus lactis subsp. lactis Il1403 are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1627' rel='noopener noreferrer' target='_blank'>MTBLS1627</a>.UPLC-MS/MS assay of Bacteroides uniformis and Clostridium saccharolyticum is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1757' rel='noopener noreferrer' target='_blank'>MTBLS1757</a>.UPLC-MS/MS assay of Clostridium saccharolyticum, Escherichia coli ED1a, Escherichia coli IAI1, Lactobacillus plantarum WCFS1, Lactococcus lactis subsp. lactis Il1403 and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1791' rel='noopener noreferrer' target='_blank'>MTBLS1791</a>.UPLC-MS/MS assay of Eubacterium rectale and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1792' rel='noopener noreferrer' target='_blank'>MTBLS1792</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and standards is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS2885' rel='noopener noreferrer' target='_blank'>MTBLS2885</a>.

Project description:Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of 15 structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before.Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine.Taken together, bioaccumulation by gut bacteria might be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner. Linked studies;UPLC-MS/MS assays of Bifidobacterium animalis subsp. lactis are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1264' rel='noopener noreferrer' target='_blank'>MTBLS1264</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and Escherichia coli IAI1 is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1319' rel='noopener noreferrer' target='_blank'>MTBLS1319</a>.UPLC-MS/MS assays of Escherichia coli ED1a, Clostridium saccharolyticum, Escherichia coli IAI1, Streptococcus salivarius, Eubacterium rectale, Lactobacillus plantarum WCFS1 and Lactococcus lactis subsp. lactis Il1403 are reported in<a href='https://www.ebi.ac.uk/metabolights/MTBLS1627' rel='noopener noreferrer' target='_blank'> MTBLS1627</a>.UPLC-MS/MS assay of Bacteroides uniformis and Clostridium saccharolyticum is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1757' rel='noopener noreferrer' target='_blank'>MTBLS1757</a>.UPLC-MS/MS assay of Eubacterium rectale and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1792' rel='noopener noreferrer' target='_blank'>MTBLS1792</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and standards is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS2885' rel='noopener noreferrer' target='_blank'>MTBLS2885</a>.

Project description:Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of 15 structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before.Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine.Taken together, bioaccumulation by gut bacteria might be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner. Linked studies;UPLC-MS/MS assays of Bifidobacterium animalis subsp. lactis are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1264' rel='noopener noreferrer' target='_blank'>MTBLS1264</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and Escherichia coli IAI1 is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1319' rel='noopener noreferrer' target='_blank'>MTBLS1319</a>.UPLC-MS/MS assay of Bacteroides uniformis and Clostridium saccharolyticum is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1757' rel='noopener noreferrer' target='_blank'>MTBLS1757</a>.UPLC-MS/MS assay of Clostridium saccharolyticum, Escherichia coli ED1a, Escherichia coli IAI1, Lactobacillus plantarum WCFS1, Lactococcus lactis subsp. lactis Il1403 and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1791' rel='noopener noreferrer' target='_blank'>MTBLS1791</a>.UPLC-MS/MS assay of Eubacterium rectale and Streptococcus salivarius is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1792' rel='noopener noreferrer' target='_blank'>MTBLS1792</a>.UPLC-MS/MS assay of Lacrimispora saccharolytica and standards is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS2885' rel='noopener noreferrer' target='_blank'>MTBLS2885</a>.