 The proposed research will exploit our proven capability to use high-throughput molecular genomic techniques to define the intestinal microbiome in order to help define the role of the gut microbiota in chronic constipation and will explore the potential value of altering the microbiota as a management strategy in constipation. The linkage of high-throughput genomic analyses with cause-and-effect understanding of how the gut microbiota affects bowel function may lead to a reliable means to manage the gut microbiota with the intent to prevent andor treat constipation. The immediate goals of this project are to expand on existing information about the microbial ecology in the human intestines focusing on its relationship with constipation using molecular microbiological techniques and to assess the effects on the gut microorganisms resulting from the use of the FDA-approved medication, lubiprostone. Lubiprostone is a member of a novel therapeutic class called prostones and is an orally active, bicyclic fatty acid that selectively acts on type 2 chloride channels to stimulate chloride secretion which induces a net increase in luminal fluid secretion. Unlike antibiotic, probiotic and prebiotic agents, it has no known direct effects on the gut microbiota. It is FDA-approved for the treatment of chronic constipation in men and women and for women with constipation-predominant IBS C-IBS. The rationale for using lubiprostone to modify the gut microbiota stems from the use of similar strategies for controlling recalcitrant small intestinal bacterial overgrowth i.e., altering fluid fluxes in the gut lumen. 