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