Grant: CIHR Fellowship

The gastrointestinal tract is home to trillions of microorganisms, collectively called the gut microbiome, that have a profound impact on human health. It remains unclear, however, the extent to which these microbes can interfere with the treatment of human disease by metabolizing therapeutic drugs within the gut. One particular species of bacteria that can be present in the gut, Eggerthella lenta (E. lenta), is able to inactivate the cardiac drug digoxin, interfering with its efficacy in the treatment of patients with heart disease. We propose to use this organism, and its drug metabolism ability, as a model for developing tools to target specific bacteria or activities in the gut. To do this, we will engineer viruses to carry elements that interact with the E. lenta adaptive immune system to inhibit drug metabolism, and subsequently use the viruses to infect E. lenta within the gastrointestinal tract. We hope to show that the strategy used for E. lenta and cardiac drug metabolism can be generalized, and that other species, strains, or activities in the gut microbiome can be manipulated in this manner for therapeutic purposes. This work is important in the gut microbiome field because there is currently no tool for specific targeting of bacterial species or activities within this complex environment. The development of a method to easily manipulate specific microbes or control their metabolism could improve treatment outcomes for patients who carry drug-metabolizing strains of bacteria, bringing us closer toward the goal of precision medicine.