Bioaccumulation of therapeutic agents by human intestinal bacteria

Klünemann, M., Andrejev, S., Blasche, S. et al. Bioaccumulation of therapeutic agents by human enteric bacteria. Nature (2021). https://doi.org/10.1038/s41586-021-03891-8

Commentary

This study investigated the availability and efficacy of gut bacteria and therapeutic agents.

It was found that systematic mapping of drug-bacteria interactions has only recently begun, with the main underlying mechanism proposed being the chemical transformation of drugs by microbes (biotransformation).

The study investigated the depletion of 15 structurally diverse drugs by 25 representative strains of intestinal bacteria and revealed 70 bacteria-drug interactions, 29 of which had not been previously reported.

More than half of the new interactions can be attributed to bioaccumulation, bacteria that store drugs intracellularly without chemically modifying them or affecting bacterial growth.

As a good example, we used click chemistry, thermal proteome profiling, and metabolomics to study the molecular basis of bioaccumulation of the widely used antidepressant drug duloxetine.

They found that duloxetine binds to several metabolic enzymes and alters the secretion of metabolites in each bacterium.

When tested in accumulator and non-accumulator defined microbial communities, duloxetine significantly altered community composition through metabolic cross-feeding, and the researchers validated this finding in animal models, showing that bioaccumulative bacteria weakened behavioral responses.

And the results indicated that bioaccumulation by gut bacteria may be a general mechanism that alters drug availability and bacterial metabolism, affecting microflora composition, pharmacokinetics, side effects, and drug response in individual ways.