Host control of the enteric microbiota during the postnatal period

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In the adult host, the enteric microbiota represents a complex, dense and competitive microbial ecosystem with the capacity to reconstitute after transient disturbance and to out-compete colonization by orally acquired bacteria. In contrast, the enteric microbiota of the neonate is largely determined by environmental exposure and exogenous factors. Although high bacterial numbers are reached shortly after birth, it displays a large individual variation and allows colonization by exogenous bacteria. The postnatal phase represents a critical period in the development of the mucosal immune system. Alterations of the newborn’s environmental exposure in industrialized countries with potential major influence on the microbiota are discussed in the hygiene hypothesis to contribute to the recent rise in the incidence of inflammatory diseases. Although mucosal host factors were shown to influence bacterial colonization, their nature and functional importance for the postnatal development of the microbiota are largely unknown. Using models of competitive colonization with commensal and pathogenic bacteria in both conventional and germ-free neonate mice, the proposed research project aims at the identification, characterization and functional analysis of inducible and developmental factors that drive the establishment of the enteric microbiota after birth and provide protection from pathogen colonization and infection.The research project addresses the following three issues:(i) The kinetic and exogenous modulators of postnatal bacterial colonization of the mouse intestine.(ii) Inducible host factors that influence the postnatal microbiota, colonization resistance and infection susceptibility.(iii) Developmentally regulated host factors and their effect on bacterial colonization and infection susceptibility.The results are expected to provide a better understanding of the processes involved to establish (and maintain) the enteric microbiota and to identify new strategies to reinforce colonization resistance and intestinal host-microbial homeostasis.