ECCMID 2019 - Human-targeted, non-antibiotic drugs impact commensal gut bacteria

  • Jackie Johnson
  • Conference Reports
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A study in Nature showed that in patients with type II diabetes, metformin treatment induced gut microbial composition changes1.Although there have been similar studies where changes to the microbiome could be linked to non-antibiotic drugs, the number of non-antibiotic drugs on the market is in the thousands, and there is still little knowledge as to how these drugs can impact the gut. Most studies are correlative, and specific drug-bacteria interactions are largely unknown.

These studies, presented by Kiran R. Patil 2, aimed to move from correlations to more precise mechanisms of ‘drug–bug’ interactions, and to elucidate complex community level data. To this end, investigators used several in vitro microbiomic single bug screens and community screens to identify direct drug–bug interactions. One screen tested the Prestwick chemical library of 1200 drugs on 40 representative human gut isolates with 38 representative species—in total directly analysing 48,000 drug–strain pairs.

A substantial fraction of human-targeted drugs impacted commensal gut bacteria, with nearly one quarter of non-antibiotic drugs inhibiting growth of at least one commensal species. In some cases, this may explain drug side effects. Secondly, commensal bacteria that were sensitive to non-antibiotic drugs were also sensitive to antibiotics, and the more abundant commensal bacteria were more affected by human-targeted drugs.

Investigators also found that some anti-depressant drugs, including Duloxetine, were subject to bio-accumulation by gut bacteria. This appears to be a widespread yet under-appreciated phenomenon with relevance for drug efficacy and pharmacokinetic studies.

Patil emphasised that these results suggest that non-antibiotic drug treatments could result in community-level disruption of the gut microbiome, though additional studies are ongoing.

Expert commentary:

Question: ‘Do we have to think about probiotic approaches when taking non-antibiotic medications?’

Answer: ‘One approach could be probiotics. The second approach could be drug combinations to modulate these effects.  It doesn’t have to be a drug per se, it could also be a food compound.’