Senior Scholar Award in Global Infectious Disease
David A. Relman, M.D.
Stanford University School of Medicine, VA Palo Alto Health Care System

The Human Intestinal Microbiome: Community Analysis, Host Response, and Role in Chronic Disease

Our understanding of the microorganisms that inhabit the human body is woefully inadequate. The diversity, abundance, and activities of these microorganisms are all matters of both importance and ignorance. This might seem surprising given that the human body contains far more microbial cells than it contains human cells. The repercussions of our information deficit are extensive: many of these poorly-characterized microbes probably play critical roles in maintaining human health, and some microbes, both transient and permanent members of our microflora, play necessary roles in disease. In particular, compelling evidence suggests that disruption of the endogenous intestinal microbial ecosystem contributes to a number of diseases, such as inflammatory bowel disease, tropical and celiac sprue and antibiotic-associated diarrhea, with major impact on global health. Much of the current situation can be attributed to a historical and conceptual dependence on cultivation-based methods for recognizing and characterizing microorganisms. But scientific developments during the past decade have led to a new set of tools for detecting, classifying, and assessing the function of single microorganisms and microbial communities. As a result, human microbial ecology and pathogen discovery have experienced a re-birth and are benefiting from new scientific perspective.

The goals of the proposed work are to characterize human intestinal microbial communities (microbiome: the collection or collectivity of microorganisms) using molecular methods, examine the mechanisms of interaction between host and microbiome using genomic approaches, and determine how the microbiome both preserves local health and promotes pathology. We will focus on inflammatory bowel disease, tropical and celiac sprue, antibiotic-associated diarrhea, as well as states of health. The composition of the associated microbiome will be assessed based on ribosomal DNA and RNA sequences, and attention will be given to richness (diversity), evenness (relative abundance), and variation with respect to time, person, and anatomic niche. Host response at the adjacent mucosal surface will be assessed based on genome-wide gene statement patterns. Correlations between microbiome composition and host response may predict future clinical events, provide novel diagnostic signatures, as well as provide new insights into mechanisms of disease.

Contact Dr. Relman.