About me
Michael Shamash, Tommy Boutin, Ezrah Isaac Roy, Laura Carolina Camelo Valera, Corinne F Maurice
Delayed development of the gut bacteriome and virome in a human microbiota-associated mouse model of malnutrition
The human gut microbiota, a dense community of microorganisms residing in the gastrointestinal tract, assembles according to a defined developmental program during the first 1,000 days of life. Many chronic conditions are causally associated with impaired gut microbiome development, including childhood stunting. We developed a human microbiota-associated mouse model of early life malnutrition providing the experimental framework to test phage-driven remodeling of the gut microbiota during this crucial period. Mice inoculated with feces from stunted infant donors and maintained on a deficient diet gave birth to pups which were 40% lighter and 25% shorter at weaning. Regular fecal sampling of breeders and pups allowed us to track colonization dynamics and vertical transmission of bacterial and viral taxa. Fecal samples were processed for bacterial and viral metagenomics using a combination of amplicon, shotgun, and proximity-ligation (“Hi-C”) sequencing. Despite robust bacterial colonization in mice, colonization of viral operational taxonomic units (vOTUs) was more variable, resulting in virome compositions distinct from those of the human donors. When comparing phage-host predictions from iPHoP, a recently developed bioinformatic tool, to our proximity-ligation dataset, over 90% of phage-host predictions were concordant at the phylum-, class-, order-, and family-levels. Using the family-level predicted host for vOTUs as a functional metric of virome diversity, we modeled virome development in pups, revealing health-dependent colonization dynamics. Ongoing experiments are evaluating the effects of fecal virome transplants in promoting healthy microbiome development of malnourished pups.
