Advancing the understanding of beneficial bacteria that prevent infections in immunocompromised pediatric patients
All humans are coated in complex populations of microbes that constitute the microbiota and contain beneficial bacteria, known as commensal bacteria. Some of these beneficial bacteria play a role in infection prevention by enhancing human immune defenses or preventing the invasion and colonization of potentially harmful (e.g. highly antibiotic-resistant) bacteria. The main goal of our laboratory is to advance our understanding of the interactions within the bacteria community, specifically those between beneficial bacteria and their mammalian hosts. Our work uses computational and laboratory-based projects to identify commensal bacteria that could prevent infections in immunocompromised pediatric patients.
To advance our understanding of commensal bacteria, we take a multifaceted research approach. Our laboratory moves between large human datasets and in vivo and in vitro model systems to study the pediatric microbiota, host-bacterial interactions, and response to cancer/antibiotic treatment. By examining these areas, we are able to discover and exploit beneficial bacteria that reduce the risk of infection by highly antibiotic resistant bacteria in immunocompromised pediatric patients.
Normal physiological and immunological functions of pediatric microbial communities
One of our primary interests is to understand how pediatric microbial communities develop and alter from infancy to early adulthood. If we can understand what happens during normal development in these communities, we can begin to understand what happens in these communities when disturbances occur. We consider the following questions as we conduct work in this area.
How does the metabolic potential of gut, oral, and nasal microbiomes alter over infancy and childhood?
What is the impact of infant diet (breast milk versus formula) on host-microbial interactions such as vaccine responses?
Does a host’s age impact efficiency of fecal-microbiome transplants?
Evaluation of microbial colonization resistance mechanisms to multi-drug resistant bacteria
Due to the various treatments St. Jude patients receive, our patient population has a high likelihood of possessing multi-drug resistant bacteria. A patient’s response to cancer and antibiotic treatment may alter their microbial communities, which alters the likelihood they have a multi-drug resistant organism. In response to this increased likelihood, we seek to understand how some commensal bacteria can crowd-out or inhibit multi-drug resistant bacteria.
Our work strives to determine the mechanisms that prevent or allow multi-drug resistant bacteria to dominate commensal bacterial communities of immunocompromised pediatric patients. Beyond antibiotic use, we seek to understand what other factors determine which resistance genes occur in human-associated bacterial communities.
Impact of different disturbances on the composition of microbial communities in immunocompromised pediatric patients
Because of the various clinical treatments St. Jude patients undergo—such as diet and antibiotic changes, radiation, chemotherapy, etc.—we seek to understand how these disturbances alter the composition of a patient’s microbial community. By determining the cause(s) of microbial community changes—whether it be changes in response to cancer or antibiotic treatment—our aim is to increase our understanding of what these changes mean. A key consideration in this area of study is whether alterations in these communities are good markers to estimate cancer and sickle cell anemia outcomes.
All our work begins with the analysis of expansive human datasets, which allows us to guide our in vivo and in vitro experiments where we work to establish a functional understanding of how the host and bacteria interact in normal and immunocompromised environments. We conduct a global examination of all bacteria, with a particular interest in how they can impact Clostridium difficile infections and colonization with vancomycin-resistant Enterococcus.
Our work demands we take an interactive approach and as a result, our research efforts span multiple disciplines. But it is our extensive collaboration with clinicians at St. Jude that serves as the defining hallmark of our work.
Ellie Margolis, MD, PhD
Department of Infectious Diseases
MS 320, Room E8002
St. Jude Children's Research Hospital