Clinical Research Directory

Study of the Ecological and Evolutionary Dynamics of Escherichia Coli in the Digestive Commensal Flora

Sponsor: Assistance Publique - Hôpitaux de Paris

Summary

Escherichia coli (E. coli) poses a major public health problem. E. coli is not only a commensal of the digestive tract but also a major opportunistic pathogen, first cause of urinary tract infections, first cause of bacteremia. However, little is known about the dynamics of intestinal colonization of the human host. Understanding the dynamics of colonization is crucial because selection for the major traits of E. coli is antibiotic resistance and virulence (the propensity to cause infection) works in commensalism, in the gut, not in infections. This study will make possible for the first time to study the colonization dynamics of E. coli in a large healthy host population. The main objective is to quantify the succession (gain, loss or replacement) of E. coli strains in the gut microbiota in healthy volunteers and how it depends on the properties of the host and the bacteria. This study will thus provide a better understanding of the E. Coli's epidemiological dynamics and the development of certain traits such as antibiotic resistance. To reach this goal, the study will take place in two successive phases : A first pilot phase will first be conducted with 50 healthy volunteers. During this pilot phase, a stool sample will be taken. The strains isolated during this pilot phase will be sequenced, making possible to characterize the strains present and the strains' possible changes between two stool samples. Succession rates will be estimated. The optimal sampling rate that maximizes accuracy in estimating succession rates will be identified and retained for the second phase. A second phase, a prospective cohort study will also be conducted in 200 healthy volunteers. During this second phase, healthy volunteers who participated in the first phase will be able to continue their participation and new volunteers will be selected. The healthy volunteers included in the prospective cohort study will be followed up with visits and stool samples which will be defined according to the results of the pilot phase.

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