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- The availability and efficacy of therapeutic drugs can be regulated by gut bacteria.
- However, the systemic mapping of the drug-bacteria interactions has only started recently.
- The primary underlying mechanism suggested is that microorganisms chemically transform drugs in the process called biotransformation.
- Researchers investigated the reduction of 15 structurally diverse drugs by 25 representative strains of bacteria in the gut.
- The study was led by researchers from the Medical Research Council Toxicology Unit at the University of Cambridge and the European Molecular Biology Laboratory in Heidelberg, Germany.
- Researchers discovered 70 bacteria-drug interactions.
- 29 of the 70 bacteria-drug interactions had not been reported.
- More than 50 percent of the new interactions can be attributed to bioaccumulation.
- In this context, bioaccumulation occurs when bacteria store the drug intracellularly without chemically modifying it.
- Most of the time, bioaccumulation does not affect the growth of the bacteria.
- Common drugs can accumulate in gut bacteria which can alter bacterial function and reduce drug effectiveness.
- This interaction could help scientists better understand individual differences in drug responses.
- Researchers studied the molecular basis of bioaccumulation of the widely used drug called duloxetine by using click chemistry, thermal proteome profiling, and metabolomics.
- Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor antidepressant which is used to treat major depressive disorder in adults.[2]
- Researchers found that duloxetine binds to several metabolic enzymes and affects the metabolite secretion of the respective bacteria.
- The study used defined microbial community of accumulators and non-accumulators and found that duloxetine altered the composition of the community through metabolic cross-feeding.
- Metabolic cross-feeding is defined as the interaction between bacterial strains in which molecules resulting from the metabolism of one strain are further metabolised by another strain.[3]
- Researchers further validated their findings by using an animal model and found that bacterial bioaccumulation reduces the behavioral response of Caenorhabditis elegans to duloxetine.
- In contrast, C. elegans with bacteria that did not accumulate duloxetine showed no behavioral changes.
- C. elegans is a nematode worm commonly used to study gut bacteria.
- The results suggest that bioaccumulation by bacteria in the gut may be a common mechanism that affects drug availability and bacterial metabolism.
- Additionally, gut bacterial bioaccumulation can have an effect on microbiota composition, pharmacokinetics, side effects, and drug response, perhaps in an individual manner.
Sources:
Klünemann, M., Andrejev, S., Blasche, S., Mateus, A., Phapale, P., Devendran, S., Vappiani, J., Simon, B., Scott, T. A., Kafkia, E., Konstantinidis, D., Zirngibl, K., Mastrorilli, E., Banzhaf, M., Mackmull, M. T., Hövelmann, F., Nesme, L., Brochado, A. R., Maier, L., Bock, T., … Patil, K. R. (2021). Bioaccumulation of therapeutic drugs by human gut bacteria. Nature, 10.1038/s41586-021-03891-8. Advance online publication. https://doi.org/10.1038/s41586-021-03891-8
https://www.nature.com/articles/s41586-021-03891-8
[2] https://www.drugs.com/duloxetine.html
[3] https://www.frontiersin.org/articles/10.3389/fevo.2019.00153/full
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