Tuesday, November 28, 2017   |   through Tuesday, November 28, 2017   |   4pm   |   HSB T-739   |   Speaker: Dr. B. Brett Finlay, OC, OBC, FRSC, FCAHS

"Role of the Microbiota in Asthma and Malnutrition"

The past decade has seen an explosion in knowledge about the microbes that live in and on us, and their role in human health and disease.  Asthma is an inflammatory disease of the lungs whose incidence is increasing rapidly, making it a major problem worldwide.  Although the exact cause is not known, environmental conditions such as the use of antibiotics, mode of delivery, etc. impact on asthma.  We have shown that early life microbiota is critical for determining asthma outcome. Using clinical cohorts of children from Canada and Ecuador, we have identified particular microbiota, including a yeast, that play a profound impact asthma susceptibility. A subclinical chronic inflammatory disease of the small intestine called environmental enteropathy (EE) is now recognized as the major contributor to childhood malnutrition. Features of EE include growth stunting, intestinal permeability, villous blunting and intestinal inflammation independent of any known infectious etiology. EE has a profound impact on the persistence of childhood malnutrition even after dietary intervention, yet to date no preclinical models of EE exist. We found that, in mice, early life consumption of a malnourished diet, in combination with exposure to a cocktail of Bacteroidales and E. coli species, remodels the small intestine to resemble the major features of EE observed in humans. We also found that the brain microglial cells are affected in this model.  Collectively, these studies demonstrate that early life microbiota play major roles in childhood health, including malnutrition and asthma.

Tuesday, December 5, 2017   |   through Tuesday, December 5, 2017   |   4pm   |   HSB T739   |   Speaker: Michael S. Gilmore, PhD

"Multidrug resistant Enterococci, a problem foreordained by events of the Paleozoic era"

Enterococci are among the most widely distributed core components of gut flora in animals from invertebrates and insects to mammals. This led us to speculate that an ancestral Enterococcus colonized the last common ancestor, and was vertically disseminated as new host species evolved. Despite being numerically minor constituents of the gut microbiota, enterococci emerged among the vanguard of multidrug resistant hospital adapted pathogens. Interestingly this happened twice: in Enterococcus faecalis, and in the distantly related species E. faecium. This raises two questions: 1) What are the core properties of enterococci that make them nearly universal components of gut consortia of such a diverse range of animals? and 2) Why, among the great diversity of gut microbes, did enterococci repeatedly emerge to become leading causes of multidrug resistant hospital acquired infection? With antibiotic resistance now a leading global public health threat, there is a compelling need to understand the underlying biology and genetics that led to their hospital adaptation.

To determine the core traits of enterococci that both enable them to inhabit animals with diverse gut physiologies and diets, and predisposed them to adapt and proliferate in the modern hospital ecology, we selected 25 enterococcal species representing all major phylogenetic branches of the genus. We examined them in detail for phenotype, genotype, and where possible, correlated that with host association. We further compared these traits to those of both commensal and multidrug resistant strains of the most common human associated species, E. faecalis and E. faecium. We found that the enterococci acquired the ability to withstand episodic desiccation and starvation, among other stressors, and that speciation is largely driven by changing carbohydrates available in the gut of new hosts. Calibration of divergence indicates that enterococci arose commensurate with the terrestrialization of animals, and parallels their radiation, including gaps as occurred during the Permian Extinction. In adapting to cycles of deposition on land, the enterococci acquired traits that positioned them well for survival and adaptation to the modern hospital environment.