The role of the virome in the metabolic landscape of the neonate gut microbiome

Though bacteriophages are abundant in the gut, an understanding of their importance to the microbiome is lacking. Phages may control populations, contribute to dysbiosis, and facilitate horizontal gene transfer. They also offer a targeted means to modulate the microbiota (i.e. phage therapy). Phages are present from the beginning of life and are dynamic in the infant gut. Additionally, phages preferentially bind to mucus, which may help to keep bacteria from penetrating host tissue and inducing inflammation.

Aim: To test the hypothesis that bacteriophages regulate the composition and metabolome of the microbiota and mediate colonization of the mucus layer.

Approach: 1. Profile phage composition and dynamics in an established cohort of extremely-low birth weight premature neonates. Stool collected from longitudinal sampling of neonates will beanalyzed using long-read sequencing (e.g. PacBio, MinION) with T. Rattei to characterize phages in the infant gut. 2: Isolate phages and their bacterial hosts for detailed genome-based characterization, evaluation of host range, and for experimental work in 3. 3: Evaluate the importance of phages for the microbiome and metabolite landscape using gnotobiotic mice (in collaboration with T. Clavel, Gunda Köllensperger). Mice will be colonized with bacterial isolates either with or without isolated phages. The composition and dynamics of the microbiome and metabolome will be evaluated by sequencing and untargeted MS. Colonization and penetration of the mucus layer will be determined using microscopy-based methods.

Relevance: This project will give insights into the importance of phages in shaping the gut microbiome/metabolome in premature neonates, a population highly vulnerable to enteric infection. It may suggest future options for modulating the microbiota and reducing infections via phage-based therapies.

Student: Lisa Madl

Faculty: Berry (PI), Loy, Köllensperger, Rattei

Funding: FWF doc.fund project MAINTAIN

Selected Publications:

Mirzaei, M. K. & Maurice, C. F. Ménage à trois in the human gut: interactions between host, bacteria and phages. Nat. Rev. Microbiol. 15, 397–408 (2017).

Sharon, I., Morowitz, M. J., Thomas, B. C., Costello, E. K., Relman, D. A. & Banfield, J. F. Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization. Genome Res. 23, 111–120 (2013).

Barr, J. J., Auro, R., Furlan, M., Whiteson, K. L., Erb, M. L., Pogliano, J., Stotland, A., Wolkowicz, R., Cutting, A. S., Doran, K. S., Salamon, P., Youle, M. & Rohwer, F. Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc. Natl. Acad. Sci. U. S. A. 110, 10771–10776 (2013).