C2
Function and Life History

Effects of malnutrition on epithelia-microbe interactions in the intestinal tract of flies and mice

The C2 project focuses on the interaction of nutritional intake with the resident microbiome and the intestinal mucosa. It uses two complementary experimental systems (mouse (C2.1, PI Rosenstiel) and Drosophila (C2.2, PI Roeder)) to tackle the same scientific problems.

A key observation is that alterations of this tripartite interaction (e.g. during malnutrition) have an influence on the immunological integrity of the mucosal barrier and change responses of the host. We will follow observations from both subprojects that have been obtained during the first funding period. Phases of malnourishment have lasting “memory” effects on both host and microbiota and we will delineate molecular mechanisms that are responsible for the long-term shifts of gene expression and cellular programs.

In a second part of the project, we will pursue the hypothesis that ageing effects are partially mediated by a complex interaction of microbiota and (endogenous) malabsorption, which reflects a similar scenario as observed in exogenous protein energy malnutrition (PEM).

We will continue with our main focus on the intestinal epithelium as a mediator between the microbiota, environmental influences (i.e. dietary factors) and the host, but also investigate the communication of the epithelium with different other cell types, in which the lasting changes occur (e.g. immune cells, insulin producing cells). We will employ innovative tools and methods such as conditional transgenic animals to elucidate the epigenetic machinery in specific cell types and single cell sequencing to delineate the exact molecular changes imprinted by PEM in vulnerable phases of development.

C2
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C2.1: Effects of malnutrition on epithelia-microbe interactions in the intestinal tract of flies

C2.2: Effects of malnutrition on epithelia-microbe interactions in the intestinal tract of mice

C2: Alumni

C2
Related Publications

Related Publications

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2020
C2

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

2020
C2

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), 12:1172, doi:10.3390/nu12041172

2020
C2

FAMIN 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

2020
C2

Adrenergic 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

2020
C2

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
C2

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

2019
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INF

Advancing 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

 

2019
C2

Dietary 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

2019
C2

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

2019
A1
C2

Prdx4 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.

2019
A4
B1
C2

A 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

2019
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A2
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INF
Z3

Comparative 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

2019
A4
B1
C1
C2

Temperature 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

2019
C2

A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine

von Frieling J, Naeem Faisal M, Sporn F, Pfefferkorn R, Nolte SS, Sommer F, Rosenstiel P, Roeder T (2019)
2019
C2

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

2019
C2

Epithelial 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
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B2
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INF
Z2

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

2018
C2
Z3

ATG16L1 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

2018
A2
C2

Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development

Franke A, Schultze JL, Bäckhed F, Rosenstiel P (2018) Genome Med. 10(1):27. doi: 10.1186/s13073-018-0534-5.
2018
C2

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

2018
C2
Z3

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

2018
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C1
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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

2018
C2
Z3

Neonatal 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

2018
A2
C2
INF
Z3

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

2018
A2
C2
INF
Z3

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

2018
C2

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
C2

Drosophila Fecal Sampling.

Christine Fink, Jakob von Frieling, Mirjam Knop, Thomas Roeder (2017); Bio-protocols, 7(18):e2547. doi: 10.21769/BioProtoc.2547

2017
C2

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

2017
C2
Z3

The 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

2017
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Efficacy 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
C2

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

2016
C2
Z3

Enterococcus 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

2016
A2
C2
INF
Z3

Genome-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

2016
C2
Z3

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

2016
C2

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

2016
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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

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