Editors' ChoiceInfectious Disease

A proactive charcoal approach shields the gut microbiome from systemic antibiotics

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Science Translational Medicine  28 Feb 2018:
Vol. 10, Issue 430, eaas8966
DOI: 10.1126/scitranslmed.aas8966

Abstract

A new activated charcoal agent protects beneficial gut microbiota from the adverse effects of systemic antibiotic therapy.

Antibiotics are a cornerstone of modern healthcare. They allow for survival from otherwise fatal infections and enable fundamental medical procedures, such as surgery and cancer chemotherapy. Systemic antibiotic treatment, while potentially lifesaving, can devastate the commensal microbes that are essential for functions ranging from immune defense to nutrient metabolism. Disruption of these microbial populations by off-target effects of antibiotics can lead to the outgrowth of Clostridium difficile and selects for drug-resistant pathogens that can disseminate within a patient or throughout a community.

Gunzberg and colleagues directly address this important issue by showing that deployment of an activated charcoal adsorbent called DAV132 to the intestine shields beneficial human microbiota from the ill effects of systemic antibiotic treatment. They test this compound in a randomized clinical trial involving 28 healthy volunteers treated with the broad-spectrum antibiotic moxifloxacin alone or in combination with the agent. DAV132 coadministration dramatically reduced undesired intestinal antibiotic levels by over 99% without eliciting any adverse side effects. Importantly, they found that DAV132 did not impact plasma concentrations of moxifloxacin, ensuring that antibiotics would still maintain full activity against a patient’s infection. Through formulation allowing directed release in the large intestine, the authors successfully developed an activated charcoal agent with gut-specific drug sequestration efficacy in a human population.

The authors extended their clinical findings by using shotgun metagenomic sequencing to molecularly characterize the effects of DAV132 administration on the intestinal microbiome. They found that while moxifloxacin eviscerated the gene richness of enteric microbial communities, DAV132 administration offered durable protection against this assault. Last, the authors confirmed using an ex vivo model that DAV132 activity was not just limited to moxifloxacin but protective against a wide range of antibiotic classes.

The small sample size of this study and the absence of data on DAV132 efficacy in a true patient population precluded confirming whether DAV132 will offer clinical benefit. Future work will be needed to prospectively validate these intriguing findings in larger clinical cohort and answer important outstanding questions such as whether DAV132 can reduce the incidence of C. difficile infection during antibiotic treatment and prevent the emergence of drug resistant microbes during long-term antibiotic therapy.

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