Effects of malnutrition on epithelia-microbe interactions in the intestinal tract of flies and mice
Maintaining the composition of the beneficial intestinal microbiota requires a homeostatic equilibrium between the microbial community and the intestinal epithelium that serves as the regulatory interface with the host. Nutritional stressors such as malnutrition, starvation or caloric restriction are believed to disturb this equilibrium, thus provoking changes in the intestinal microbiota’s composition as well as in the regenerative capacity and immunological homeostasis of the intestinal mucosa. While malnutrition is a major scourge in developing countries, caloric restriction is believed to deploy positive effects on various health-associated parameters including life span.
We aim to elucidate the mechanisms underlying this complex tripartite interplay between microbiota, the intestinal epithelium and the environment (nutritional stressors). More precisely, we want to discover how malnutrition and caloric restriction translate into the corresponding host phenotypes and how the microbiota and the intestinal epithelial reaction contribute to this, or how this influences stem cell behavior, the innate immune repertoire, transcriptional programs and lineage decisions in the epithelium.
To achieve these goals, we will use mice and Drosophila as highly versatile experimental model metaorganisms to benefit from their overlapping and complementary inherent strengths. We will combine manipulation of the microbiota with concurrent analysis of the intestinal epithelial response, which will be supplemented by the reciprocal experimental design. These studies will be performed under different nutritional regimes (e.g. malnutrition, caloric restriction) to clarify how they affect the reciprocal interplay between microbiota and intestinal epithelium. Manipulation of the microbiota will comprise fecal transfer experiments and the use of gnotobiotic animals, while manipulation of the intestinal epithelium will be focused on system governing immune homeostasis and stem cell activity. For the latter aspect, manipulation of NF-κB-, FoxO-, and Upd3(IL6-equivalent)-mediated signaling systems will be of central importance for the proposed research program.
FeaturedThe resilience of the intestinal microbiota influences health and disease.
Sommer F, Anderson J M, Bharti R, Raes J, Rosenstiel P (2017); Nat Rev Microbiol., doi: 10.1038/nrmicro.2017.58
FeaturedEfficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection. Gastroenterology.
Ott S J, Waetzig G H, Rehman A, Moltzau-Anderson J, Bharti R, Grasis J A, Cassidy L, Tholey A, Fickenscher H, Seegert D, Rosenstiel P, Schreiber S (2017); Gastroenterology, 152(4):799-811.e7. doi: 10.1053/j.gastro.2016.11.010
Octopamine controls starvation resistance, life span and metabolic traits in Drosophila.
Li Y, Hoffmann J, Li Y, Stephano F, Bruchhaus I, Fink C, Roeder T (2016); Sci Rep., 6:35359. doi: 10.1038/srep35359
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation.
Aden K, Rehman A, Falk-Paulsen M, Secher T, Kuiper J, Tran F, Pfeuffer S, Sheibani-Tezerji R, Breuer A, Luzius A, Jentzsch M, Häsler R, Billmann-Born S, Will O, Lipinski S, Bharti R, Adolph T, Iovanna J L, Kempster S L, Blumberg R S, Schreiber S, Becher B, Chamaillard M, Kaser A, Rosenstiel P (2016); Cell Rep., 16(8):2208-18. doi: 10.1016/j.celrep.2016.07.054
Intestinal FoxO signaling is required to survive oral infection in Drosophila.
Fink C, Hoffmann J, Knop M, Li Y, Isermann K, Roeder T (2016); Mucosal Immunol., 9:927-936. doi: 10.1038/mi.2015.112
The native microbiome of the nematode Caenorhabditis elegans: Gateway to a new host-microbiome model.
Dirksen P, Marsh SA, Braker I, Heitland N, Wagner S, Nakad R, Mader S, Petersen C, Kowallik V, Rosenstiel P C, Felix M A, Schulenburg H (2016); BMC Biology, 14:38. doi:10.1186/s12915-016-0258-1