C2
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.
Researchers
Prof. Dr. Philip Rosenstiel
Alumni
Publications
2020
A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine.
von Frieling J, Faisal MN, Sporn F, Pfefferkorn R, Nolte SS, Sommer F, Rosenstiel P, Roeder T (2020) PLoS Genetics. published 26 May, doi: 10.1371/journal.pgen.1008789
Furbellow (brown algae) extract increases lifespan Drosophila by interfering with TOR-signalling.
Li Y, Romey-Glüsing R, Tahan Zadeh T, von Frieling J, Hoffmann J, Huebbe P, Bruchhaus I, Rimbach G, Fink C, Roeder T (2020) Nutrients. 12:1172, doi:10.3390/nu12041172
FeaturedFAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.
Cader MZ, de Almeida Rodrigues RP, West JA, Sewell GW, Md-Ibrahim MN, Reikine S, Sirago G, Unger LW, Iglesias-Romero AB, Ramshorn K, Haag LM, Saveljeva S, Ebel JF, Rosenstiel P, Kaneider NC, Lee JC, Lawley TD, Bradley A, Dougan G, Modis Y, Griffin JL, Kaser A (2020) Cell. 180(2):278-295.e23. doi:10.1016/j.cell.2019.12.017
FeaturedAdrenergic Signaling in Muscularis Macrophages Limits Infection-Induced Neuronal Loss.
Matheis F, Muller PA, Graves CL, Gabanyi I, Kerner ZJ, Costa-Borges D, Ahrends T, Rosenstiel P, Mucida D (2020) Cell. 180(1):64-78.e16. doi:10.1016/j.cell.2019.12.002
Autophagy of Intestinal Epithelial Cells Inhibits Colorectal Carcinogenesis Induced by Colibactin-producing Escherichia coli in Apc(Min/+) Mice.
Lucas C, Salesse L, Thi Hoang MH, Bonnet M, Sauvanet P, Larabi A, Godfraind C, Gagnière J, Pezet D, Rosenstiel P, Barnich N, Bonnet R, Dalmasso G, Nguyen HTT (2020) Gastroenterology. pii: S0016-5085(20)30006-8. doi:10.1053/j.gastro.2019.12.026
2019
Factors that affect the translation of dietary restriction into a longer life
von Frieling J, Roeder T (2019) IUBMB Life. 1-11. doi: 10.1002/iub.2224
FeaturedAdvancing our functional understanding of host–microbiota interactions: a need for new types of studies
He J, Lange J, Marinos G, Bathia J, Harris D, Soluch R, Vaibhvi V, Deines P, Hassani MA, Wagner K-S, Zapien‐Campos R, Jaspers C, Sommer F (2019) BioEssays, 1900211 (1-5). doi: 10.1002/bies.201900211
FeaturedDietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology
Sonner JK*, Keil M*, Falk-Paulsen M*, Mishra N, Rehman A, Kramer M, Deumelandt K, Röwe J, Sanghvi K, Wolf L, von Landenberg A, Wolff H, Bharti R, Oezen I, Lanz TV, Wanke F, Tang Y, Brandao I, Mohapatra SR, Epping L, Grill A, Röth R, Niesler B, Meuth SG, Opitz CA, Okun JG, Reinhardt C, Kurschus FC, Wick W, Bode HB, Rosenstiel P*, Platten M* (2019) Nat Commun. 10(1):4877. doi: 10.1038/s41467-019-12776-4. *shared first or last authorship
The microbiota promotes arterial thrombosis in low-density lipoprotein receptor-deficient mice
Kiouptsi K#, Jäckel S#, Pontarollo G#, Grill A, Kuijpers MJE, Wilms E, Weber C, Sommer F, Nagy M, Neideck C, Jansen Y, Ascher S, Formes H, Karwot C, Bayer F, Kollar B, Subramaniam S, Molitor M, Wenzel P, Rosenstiel P, Todorov H, Gerber S, Walter U, Jurk K, Heemskerk JWM, van der Vorst EPC#, Döring Y#, Reinhardt C (2019) mBio. 10(5). doi: 10.1128/mBio.02298-19. # Contributed equally
FeaturedPrdx4 limits caspase-1 activation and restricts inflammasome-mediated signaling by extracellular vesicles
Lipinski S, Pfeuffer S, Arnold P, Treitz C, Aden K, Ebsen H, Falk-Paulsen M, Gisch N, Fazio A, Kuiper J, Luzius A, Billmann-Born S, Schreiber S, Nuñez G, Beer HD, Strowig T, Lamkanfi M, Tholey A, Rosenstiel P (2019) EMBO J. 38(20) doi: 10.15252/embj.2018101266.
FeaturedA phage protein aids bacterial symbionts in eukaryote immune evasion
Jahn MT, Arkhipova K, Markert SM, Stigloher C, Lachnit T, Pita L, Kupczok A, Ribes M, Stengel ST, Rosenstiel P, Dutilh BE, Hentschel U (2019) Cell Host & Microbe, doi: 10.1016/j.chom.2019.08.019
FeaturedComparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms
Rausch P, Rühlemann M, Hermes BM, Doms S, Dagan T, Dierking K, Domin H, Fraune S, von Frieling J, Hentschel U, Heinsen F-A, Höppner M, Jahn MT, Jaspers C, Kissoyan KAB, Langfeldt D, Rehman A, Reusch TBH, Roeder T, Schmitz RA, Schulenburg H, Soluch R, Sommer F, Stukenbrock E, Weiland-Bräuer N, Rosenstiel P, Franke A, Bosch T, Baines JF (2019) Microbiome, doi: 10.1186/s40168-019-0743-1
FeaturedTemperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways
Mortzfeld BM*, Taubenheim J*, Klimovich AV, Fraune S, Rosenstiel P, Bosch TCG (2019) Nature Communications 10, 3257. doi: 10.1038/s41467-019-11136-6
A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine
Drosophila melanogaster in nutrition research—the importance of standardizing experimental diets
Lüersen K, Roeder T, Rimbach G (2019) Genes Nutr. 14: 3. doi: 10.1186/s12263-019-0627-9
FeaturedEpithelial endoplasmic reticulum stress orchestrates a protective IgA response
Joep Grootjans*, Niklas Krupka*, Shuhei Hosomi*, Juan D. Matute, Thomas Hanley, Svetlana Saveljeva, Thomas Gensollen, Jarom Heijmans, Hai Li, Julien P. Limenitakis, Stephanie C. Ganal-Vonarburg, Shengbao Suo, Adrienne M. Luoma, Yosuke Shimodaira, Jinzhi Duan, David Q. Shih, Margaret E. Conner, Jonathan N. Glickman, Gwenny M. Fuhler, Noah W. Palm, Marcel R. de Zoete, C. Janneke van der Woude, Guo-Cheng Yuan, Kai W. Wucherpfennig, Stephan R. Targan, Philip Rosenstiel, Richard A. Flavell, Kathy D. McCoy, Andrew J. Macpherson, Arthur Kaser und Richard S. Blumberg (2019) Science. DOI: 10.1126/science.aat7186
2018
Functions of the Microbiota for the Physiology of Animal Metaorganisms
Esser D, · Lange J, · Marinos G, · Sieber M, Best L, Prasse D, Bathia J, Rühlemann MC, Boersch K, Jaspers C, Sommer F (2018) J Innate Immun DOI: 10.1159/000495115
FeaturedATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING.
Aden K, Tran F, Ito G, Sheibani-Tezerji R, Lipinski S, Kuiper JW, Tschurtschenthaler M, Saveljeva S, Bhattacharyya J, Häsler R, Bartsch K, Luzius A, Jentzsch M, Falk-Paulsen M, Stengel ST, Welz L, Schwarzer R, Rabe B, Barchet W, Krautwald S, Hartmann G, Pasparakis M, Blumberg RS, Schreiber S, Kaser A, Rosenstiel P (2018); Gastroenterology. pii: jem.20171029. doi: 10.1084/jem.20171029
Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development
Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson’s disease model.
Stephano F, Nolte S, Hoffmann J, El-Kholy S, von Frieling J, Bruchhaus I, Fink C, Roeder T (2018); Sci Rep. 8(1):2372. doi: 10.1038/s41598-018-20836-w
A Drosophila model of cigarette smoke induced COPD identifies Nrf2 signaling as an expedient target for intervention.
Prange R, Thiedmann M, Bhandari A, Mishra N, Sinha A, Häsler R, Rosenstiel P, Uliczka K, Wagner C, Yildirim AÖ, Fink C, Roeder T (2018); Aging (Albany NY). 10(8):2122-2135. doi: 10.18632/aging.101536
Grow With the Challenge – Microbial Effects on Epithelial Proliferation, Carcinogenesis, and Cancer Therapy
Von Frieling J, Fink C, Hamm J, Klischies K, Forster M, Thomas C. G. Bosch TCG, Roeder T, P Rosenstiel P, Sommer F (2018); Front. Microbiol. doi: 10.3389/fmicb.2018.02020
FeaturedNeonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition.
Fulde M, Sommer F, Chassaing B, van Vorst K, Dupont A, Hensel M, Basic M, Klopfleisch R, Rosenstiel P, Bleich A, Bäckhed F, Gewirtz AT, Hornef MW (2018); Nature 560(7719):489-493. doi: 10.1038/s41586-018-0507-2
Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development.
Pan WH, Sommer F, Falk-Paulsen M, Ulas T, Best P, Fazio A, Kachroo P, Luzius A, Jentzsch M, Rehman A, Müller F, Lengauer T, Walter J, Künzel S, Baines JF, Schreiber S, Franke A, Schultze JL, Bäckhed F, Rosenstiel P (2018); Genome Med. 10(1):27. doi: 10.1186/s13073-018-0534-5
The antibiotic resistome and microbiota landscape of refugees from Syria, Iraq and Afghanistan in Germany.
Häsler R, Kautz C, Rehman A, Podschun R, Gassling V, Brzoska P, Sherlock J, Gräsner J T, Hoppenstedt G, Schubert S, Ferlinz A, Lieb W, Laudes M, Heinsen F A, Scholz J, Harmsen D, Franke A, Eisend S, Kunze T, Fickenscher H, Ott S, Rosenstiel P, Schreiber S (2018); Microbiome., 6(1):37. doi: 10.1186/s40168-018-0414-7
Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.
Romey-Glüsing R, Li Y, Hoffmann J, von Frieling J, Knop M, Pfefferkorn R, Bruchhaus I, Fink C, Roeder T (2018); FASEB J., 5:fj201700934R. doi: 10.1096/fj.201700934R
2017
Drosophila Fecal Sampling.
Christine Fink, Jakob von Frieling, Mirjam Knop, Thomas Roeder (2017); Bio-protocols, 7(18):e2547. doi: 10.21769/BioProtoc.2547
The Role of Monoaminergic Neurotransmission for Metabolic Control in the Fruit Fly Drosophila Melanogaster.
Li Y, Tiedemann L, von Frieling J, Nolte S, El-Kholy S, Stephano F, Gelhaus C, Bruchhaus I, Fink C, Roeder T (2017); Front. Syst. Neurosci., 11:60. doi: 10.3389/fnsys.2017.00060
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
2016
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
FeaturedEnterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects.
Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, Duong C P, Flament C, Lepage P, Roberti M P, Routy B, Jacquelot N, Apetoh L, Becharef S, Rusakiewicz S, Langella P, Sokol H, Kroemer G, Enot D10, Roux A, Eggermont A, Tartour E, Johannes L, Woerther P L, Chachaty E, Soria J C, Golden E, Formenti S, Plebanski M, Madondo M, Rosenstiel P, Raoult D, Cattoir V, Boneca I G, Chamaillard M, Zitvogel L (2016); Immunity., 45(4):931-943. doi: 10.1016/j.immuni.2016.09.009
FeaturedGenome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota.
Wang J, Thingholm L B, Skiecevičienė J, Rausch P, Kummen M, Hov J R, Degenhardt F, Heinsen F A, Rühlemann M C, Szymczak S, Holm K, Esko T, Sun J, Pricop-Jeckstadt M, Al-Dury S, Bohov P, Bethune J, Sommer F, Ellinghaus D, Berge R K, Hübenthal M, Koch M, Schwarz K, Rimbach G, Hübbe P, Pan W H, Sheibani-Tezerji R, Häsler R, Rosenstiel P, D’Amato M, Cloppenborg-Schmidt K, Künzel S, Laudes M, Marschall H U, Lieb W, Nöthlings U, Karlsen T H, Baines J F, Franke A (2016); Nat Genet., 48(11):1396-1406. doi: 10.1038/ng.3695
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