Bacteriophages are viruses that do not infect humans, but target specific bacteria. Because they are safe for humans and can selectively combat specific microorganisms, they are being examined for their potential to help restore balance to the microbiota.
The Bacteriophage for Gastrointestinal Health (PHAGE) Study is the first randomized, double-blind, placebo controlled cross-over trial designed to investigate the four bacteriophages (LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae) ability to modulate the microbiome and reduce gastrointestinal distress in healthy individuals. Secondary outcomes include local and systemic inflammatory markers (e.g., sIgA, TNF-a, IL-6, etc) and plasma lipid profiles.
Individuals not diagnosed with disorders but who reported significant gastrointestinal distress were enrolled into the study. Participants were assigned to either the placebo or treatment group for the first 4-weeks followed by a 2-week washout period and an additional 4-weeks on the opposite treatment. Outcome measures included evaluating shifts in the microbiota using 16S rRNA sequencing and targeted qPCR, self-assessment of gastrointestinal distress, fecal calprotectin and secretory IgA, fecal short-chain fatty acids and triglycerides, high sensitivity CRP and 13 circulating cytokines and inflammatory mediators, plasma lipid profiles, and metabolic safety markers. 32 participants completed the study. The treatment was well tolerated with no adverse events or differences in metabolic safety markers detected. Bacteriophage treatment resulted in significant decreases in IL-4, often associated with allergic response, but no other inflammatory markers. There was also a trend towards decreased total and LDL cholesterol with bacteriophage consumption; however, this significance would need to be determined in a larger more clinically relevant population. There were no major perturbations to the microbiota as indicated by alpha and beta diversity measures, suggesting that bacteriophage consumption is selective and does not globally disrupt the microbiota. Changes in differential abundance of several key bacterial species, including reductions OTU’s most closely mapping to the pathogen Clostridium perfringens, were observed.