Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption

Objective: The gut microbiota has been recognized as a critical regulator of human health, and novel interventions to selectively modulate the microbiota are actively being sought. Bacteriophages (bacterial viruses) have the potential to selectively eliminate specific detrimental microbes while enhancing beneficial microbe populations. The Bacteriophage for Gastrointestinal Health (PHAGE) study aimed to determine the safety and tolerability of supplemental bacteriophage consumption in a population of healthy adults with mild to moderate gastrointestinal distress. Methods: The PHAGE study was a randomized, double-blind, placebo-controlled crossover intervention. Healthy adults with self-reported gastrointestinal distress were recruited and asked to consume one 15-mg capsule containing 4 strains of bacteriophages (LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae) and a placebo, each for 28 days. Participants were randomly assigned to the starting treatment, which was followed by a 2-week washout period before they began the second arm of the intervention. Primary outcome measures included a comprehensive metabolic panel and gastrointestinal health questionnaire. In addition, samples were collected for future analysis of several secondary outcome measures, including global microbiota profiles, plasma lipids, and markers of local and systemic inflammation. Results: Forty-three individuals met all study criteria and consented to participate. Of these participants, 36 completed at least one arm of the trial and 32 completed the study. There were no effects of treatment sequence on comprehensive metabolic panel outcomes, but there were 1- and 2-way carryover effects on gastrointestinal questionnaire data. Levels of aspartate aminotransferase significantly decreased while participants were taking the treatment but not placebo; however, all mean values remained within clinically acceptable ranges. Participants also reported significant improvements in several symptoms of gastrointestinal distress while taking both the treatment and the placebo. Conclusions: Consumption of therapeutic doses of a mixture of 4 bacteriophages was both safe and tolerable in a target human population.