Research Interests

Research in the Young lab is directed at understanding the role of bacteria that inhabit the gastrointestinal tract and how they influence the health status of the host. To this end, we study the role of what would traditionally be considered “pathogenic bacteria” in gastrointestinal illness, with a particular emphasis on Clostridium difficile . In addition, we also examine how the population structure of the indigenous GI microbiota can influence the host-pathogen interaction and how changes in the community structure of the indigenous microbiota itself can lead to pathogenic states. This research is being conducted both with material from human subjects as well as animal models of disease.

Microbial ecology of gastrointestinal bacterial infections

Over the past decade, molecular-based approaches have revealed enormous phylogenetic diversity in the microbial world that is not yet represented in culture. This information has come almost entirely by retrieval of small subunit (SSU) rRNA sequence information, which provides a phylogenetic context in which to quantify such diversity, and typically involves cloning and sequencing the SSU rRNA-encoding gene. By comparing 16S rRNA-encoding gene sequences retrieved from complex microbial communities, the requirement for cultivation has been circumvented and we have obtained an illuminated view of the remarkable microbial diversity that is actually present in many habitats.

Clostridium difficile and the indigenous gut microbiota

About 20% of cases of antibiotic-associated diarrhea arise from infection with the toxin producing bacterial pathogen Clostridium difficile. Our published work has provided evidence that antibiotic-associated diarrhea, both cases due to infection with Clostridium difficile and cases independent of infection with this pathogen, results from the effect of antibiotics on the indigenous gut microbiota. In the case of antibiotic-associated diarrhea that develops without C. difficile infection we have provided evidence that loss of the normal fermentation capacity of the microbiota results in an osmotic diarrhea as well as potential colonic epithelial dysfunction due to decreases in the levels of short-chain fatty acids, which are the normal byproduct of bacterial fermentation. Our work on recurrent C. difficile infection has demonstrated that recurrence is associated with decreases in the overall diversity of the indigenous gut microbiota. This work provides the first evidence that alteration in the community structure of the gut microbiota can lead to sustained loss of colonization resistance against bacterial pathogens. To supplement our clinical studies, we have recently developed a murine model of C. difficile infection that recreates most aspects of human disease and allows us to closely examine the interaction between the pathogen, the indigenous microbiota and host responses in the development of disease.