Bioaccumulation of therapeutic drugs by human gut bacteria (B.animalis 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 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 MTBLS1319.

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): Diode array detection MS -

SUBMITTER: Sergej Andrejev  Kiran Patil 

PROVIDER: MTBLS1264 | MetaboLights | 2021-07-20

REPOSITORIES: MetaboLights