Nasopharynx-on-a-chip

Our knowledge of host-microbiome-pathogen interactions within the human upper respiratory tract comes largely from small, cross-sectional clinical studies. Currently, there is no model system that accurately recapitulates the complex interactions that exist between resident microbes in the nasopharynxes of children, the immune system, and exogenous pathogens. Animal models have been used to study human respiratory infections, but these models are limited by their expense and by the inability to stably colonize the upper respiratory tracts with human-derived microbes. Although experimental challenge studies have been conducted in adult populations, the vulnerability of children to invasive infections caused by bacterial respiratory pathogens and the ethics of conducting greater than minimal risk research in children has precluded these studies from being done in pediatric populations. Organ-on-a-chip models, which represent physiological organ biomimetic systems built on a microfluidic chip, represent a novel approach to studying host-microbiome-pathogen interactions.

SARS-COV-2 and the nasopharyngeal microbiome

Children are less susceptible to severe acute respiratory virus 2 (SARS-CoV-2) and typically have milder illness courses than adults; however, the factors underlying age-related differences in SARS-CoV-2 susceptibility and illness severity not well understood. As the initial site of colonization for many respiratory diseases, the upper respiratory microbiome is increasingly recognized as an important aspect of host defense against these pathogens. Thus, we are currently evaluating upper respiratory microbiome biotypes associated with SARS-CoV-2 infection susceptibility or protection in children, adolescents, and young adults that were close contacts to positive individuals.

Urbanization and the microbiome

Over the past few hundred years humans have been evolving into a primarily urban species. This evolution has coincided with an increase in allergy that may be caused by an underdeveloped immune system. Increasingly, research suggests this underdevelopment may be caused through loss of contact with beneficial, health promoting microorganisms known as the “old friends” hypothesis. This is of particular interest as humans continue to urbanize and begin spending more time indoors. Thus, it has become imperative to understand how exposure to diverse microbial populations changes the composition of the lung and gut microbiomes and whether exposure through soils results in beneficial health outcomes.