Eric G. Pamer: Antibiotics and Microbiota in Mice and Humans

Antibiotics vary in their specificity and thus can be used to selectively eliminate bacterial populations that inhabit mucosal surfaces. How the loss of different bacterial subpopulations affects the mucosal immune system is largely unknown (Figure 1). We are using the Roche-454 high-throughput sequencing platform to characterize complex microbial populations in mice and we are using this approach to investigate shifts in microbial populations in patients undergoing cancer treatment at Memorial Sloan Kettering.

Figure 1 Enlarge Image Figure 1

We have characterized antibiotic-induced changes in the intestinal microbiota and the impact on susceptibility to intestinal colonization with VRE. Antibiotic treatment decreases the density of intestinal bacteria and dramatically alters the intestinal microbiota. While mice that have not received antibiotics are resistant to colonization with VRE, antibiotic treatment enables VRE to dominate the intestinal microbiota, reaching frequencies of 95% in the ileum and cecum. Once established, VRE remains a dominant member of the microbiota upon cessation of antibiotic treatment. Characterization of the microbiota colonizing patients undergoing allogeneic hematopoietic stem cell transplantation revealed that antibiotic treatment of humans also enables VRE to dominate the intestinal microbiota.

Many questions about the relationship between the intestinal microbiota and the innate and adaptive immune systems remain unanswered and are the focus of experiments in our laboratory. The ability of different commensal microbial populations to induce resistance to intestinal pathogens and the impact of immunocompromising therapies on the composition of the intestinal microbiota are being investigated. Ongoing studies are investigating how changes in the intestinal microbiota of patients undergoing cancer therapy impact their susceptibility to infection and their response to treatment.

We have characterized antibiotic-induced changes in the intestinal microbiota and the impact on susceptibility to intestinal colonization with VRE. Antibiotic treatment decreases the density of intestinal bacteria and dramatically alters the intestinal microbiota. While mice that have not received antibiotics are resistant to colonization with VRE, antibiotic treatment enables VRE to dominate the intestinal microbiota, reaching frequencies of 95% in the ileum and cecum. Once established, VRE remains a dominant member of the microbiota upon cessation of antibiotic treatment. Characterization of the microbiota colonizing patients undergoing allogeneic hematopoietic stem cell transplantation revealed that antibiotic treatment of humans also enables VRE to dominate the intestinal microbiota.

Many questions about the relationship between the intestinal microbiota and the innate and adaptive immune systems remain unanswered and are the focus of experiments in our laboratory. The ability of different commensal microbial populations to induce resistance to intestinal pathogens and the impact of immunocompromising therapies on the composition of the intestinal microbiota are being investigated. Ongoing studies are investigating how changes in the intestinal microbiota of patients undergoing cancer therapy impact their susceptibility to infection and their response to treatment.