Our weekly Works in Progress Presentation Series.

Presenter: Armando Lerma Fuentes from the Auchtung Lab

Title: Microbial and Host Factors that Modulate Differences in Host’s Clinical Outcome to Clostridioides difficile Infection

Summary: Clostridioides difficile is one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) can fall within a wide range of disease severity from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Investigating what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms that underlie the spectrum of variation in CDI disease severity remains limited and further research is needed to determine what factors are responsible for these variations. In this work, we establish different human microbiota-associated (HMA) mouse models. By analyzing innate immune responses to CDI, we demonstrate that these models reproduce differences in disease severity during infection that were largely based on mouse strain and independent from C. difficile burden or toxin activity. Altogether, our HMA mouse models demonstrated the potential to study interactions between microbiome, pathogen and host inflammatory responses in the context of CDI.