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Multidrug-resistant bacterial infections of the gastrointestinal tract pose a serious public health concern. High levels of antibiotic drug resistance, along with the potential for antibiotics to precipitate disease or alter the gut microbiome has prompted research into alternative treatment methods. Evidence suggests that bacteriophage therapy delivered per os may be well-suited to target such infections. Areas covered: Herein, we discuss the specific advantages and challenges of using orally administered phage therapy. Our literature review encompasses recent works using phages to target various clinically-relevant bacteria in vivo. We also provide insights into methods that aim to overcome the barriers to effective phage transit through the harsh gastrointestinal environment. Expert commentary: Evidence from a number of in vivo animal studies suggests that targeting bacterial infections using phages delivered orally holds potential. Efficacious oral phage therapy depends on the delivery of sufficient phage titers to the infection site, which may be hindered by the host's gastrointestinal tract and immune response.

Cytochrome P450 2C8 (CYP2C8) epoxygenase is responsible for the metabolism of over 60 clinically relevant drugs, notably the anticancer drug Taxol (paclitaxel, PAC). Specifically, there are naturally occurring polymorphisms, CYP2C8*2 and CYP2C8*3, that display altered PAC hydroxylation rates despite these mutations not being located in the active site. Herein, we demonstrate that these polymorphisms result in a greater uncoupling of PAC metabolism by increasing the amount of hydrogen peroxide formed per PAC turnover. Anaerobic stopped-flow measurements determined that these polymorphisms have altered first electron transfer kinetics, compared to CYP2C8*1 (wildtype), that suggest electron transfer from cytochrome P450 reductase (CPR) is disfavored. Therefore, these data demonstrate that these polymorphisms affect the catalytic cycle of CYP2C8 and suggest that redox interactions with CPR are disrupted.

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