Phagineering the gut microbiome: Bacteriophages to reduce Desulfovibrio spp. and hydrogen sulfide in the intestine

Project Summary The excessive production of hydrogen sulfide (H2S) gas has been implicated in a number of health conditions including ulcerative colitis, Crohn’s disease, and colon rectal cancer due to its toxicity and inflammatory properties. While these associations have not been shown to be definitively causative, one well known fact about intestinal H2S experienced by all is its contribution to malodorous flatulence. Flatus is composed of numerous odorless gases, but primarily the presence of H2S, characterized by its sulfurous “rotten egg” aroma, provides the foul odor of flatus. For those individuals with frequent excessively odorous flatulence, it can be a debilitating and embarrassing condition. While the human body produces its own endogenous H2S, a large fraction of the exogenous H2S produced in the intestine comes from the microbiome, specifically from the sulfate-reducing bacteria (SRB). SRB utilize sulfate as their terminal electron acceptor leading to the production of the foul-smelling and toxic H2S within the gut. Of the SRB, the most predominant in the human gut are members of the genus Desulfovibrio. Sulfur-rich diets such as meat, cheese, and processed food provide fuel for SRB metabolism, and, as such, dietary protein is positively correlated with H2S production in the intestine. Due to these connections between dietary sulfur, SRB, H2S, and malodorous flatus, it is probable that a targeted reduction of Desulfovibrio spp. in the gut may lead to reduced levels of H2S and thereby less offensive odorous flatulence. A suitable form of therapy is required for this modulation: classical antibiotics are ill suited to this task as their broad-spectrum is likely to disrupt the commensal microbiota. Bacteriophages (phages) are uniquely suited to targeted modulation of the intestinal microbiome; they are natural predators of bacteria and highly specific to their hosts. This project proposes the development of natural prebiotic bacteriophage cocktail for the targeted reduction Desulfovibrio to promote overall health and well-being of the intestine, as well as reduce the malodorous scent of flatulence and its associated embarrassment. To this end, a panel of human associated Desulfovibrio isolates will be assembled. “Phage hunts” for phages infecting Desulfovibrio spp. will then be performed using methods developed as part of preliminary data generation. Isolated phages will be characterized, formulated into cocktails, and cocktail host range expanded through directed evolution. This project will be led by Dr. Justin Boeckman who will pursue a number of training courses to enhance his business acumen during the project duration. Dr. Boeckman will also be advised by valuable mentorship of Dr. Jason Gill (Technical Mentor – Texas A&M) and Dr. Neema Mayhugh (Business development- Wave Strategy) to ensure this project succeeds both on a technical and career development level.