"Throughout evolution both intestinal helminths and commensal bacteria have inhabited our intestines. This ""ménage à trois"" situation is likely to have exerted a strong selective pressure on the development of our metabolic and immune systems. Such pressures remain in developing countries, whilst the eradication of helminths in industrialized countries has shifted this evolutionary balance—possibly underlying the increased development of chronic inflammatory diseases. We hypothesize that helminth-bacterial interactions are a key determinant of healthy homeostasis.Preliminary findings from our laboratory indicate that helminth infection of mice alters the abundance and diversity of intestinal bacteria and impacts on the availability of immuno-modulatory metabolites; this altered environment correlates with a direct health advantage, protecting against inflammatory diseases such as asthma and rheumatoid arthritis. We intend to validate and extend these data in humans by performing bacterial phlyogenetic and metabolic analysis of stool samples collected from a large cohort of children living in a helminth endemic region of Ecuador. We further propose to test our hypothesis that helminth-bacterial interactions contribute to disease modulation using experimental models of infection and disease. We plan to develop and utilize mouse models to elucidate the mechanisms through which bacterial dysbiosis and helminth infection influence the development of chronic inflammatory diseases. These models will be utilized for germ-free and recolonization experiments, investigating the relative contribution of bacteria versus helminthes to host immunity, co-metabolism and disease modulation.Taking a trans-disciplinary approach, this research will break new ground in our understanding of the crosstalk and pressures between intestinal helminth infection and commensal bacterial communities, and the implications this has for human health."