Deciphering bacteria-host interaction by functional metagenomics

The human intestinal microbiota has been considered as a true organ, playing major function for its host, however little is known on the underlying mechnisms. Indeed, very few specific effectors interacting with the human host have been identified, probably due to the difficulties to cultivate most commensal bacteria. We have developped a functional metagenomic approach to identify bacterial genes and compounds regulating key signaling pathways or effector genes in human intestinal epithelial cells. Metagenomic libraries were build by cloning metagenomic DNA from 20 different donors in a fosmid vector and using E.coli as a host. A high throughput screening platform was established permitting the identification of clones modulating pathways and genes in HT-29. Although the bacterial host is a gram negative bacteria, identify genes derived from the three major phyla present in human gut, namely Firmicutes, Bacterioidetes and Actinobacteria. This functional metagenomic strategy allowed the characterization of new commensal bacteria genes and effector molecules that impact on host cellular functions with potential influence on human health.