There are clearly prospects for identifying novel intestinal microorganisms that have beneficial effects on the physiology of the host and the molecules and microbial genes involved in the mechanisms. Furthermore, metagenomic and profiling data may be used in the future as prognostic or diagnostic tools in disease prevention or treatment. In this issue of Current Opinion in Microbiology, we have brought together scientists involved in cutting-edge research to discuss the state of the art knowledge on several important facets of these complex and important scientific challenges. Our goal was to provide updates on recent advances in the crosstalk hos microbiota, and highlight the approaches and prospects for identifying and using novel microorganisms or molecules derived from the microbiota in disease prevention or treatment.