A2

Host-microbiota coevolution in the mammalian intestine

Understanding the forces that shape variation in host-associated bacterial communities within- and between host species is key to understanding the evolution and maintenance of metaorganisms.

While a multitude of studies have investigated the influence of genetic and environmental factors at the level of community profiling, little information on the underlying functional genomic basis exists. In this project, we will identify signatures of coevolution between hosts and their intestinal microbes, using a multi-tiered approach in the Western-Eastern house mouse and human-chimpanzee host species pairs. First, we will employ genetic mapping to identify host genes that vary within and/or between species and influence microbial traits. These efforts will be aided using a “systems genetics” approach by incorporating genome-wide expression data in the mouse system and molecular population genetic analysis of host genomic regions. Second, candidate bacterial group (trait) signals will be further investigated, using a combination of shotgun metagenomic sequencing and single-cell/isolate analysis to characterize them at the functional level and identify potential signatures of adaptation to their hosts.

Researchers

Dr. Femke-Anouska Heinsen

Postdoctoral Researcher, Associated Junior Researcher
Kiel University Institute of Clinical Molecular Biology

Marie Vallier

PhD Candidate, Alumni
Max-Planck-Institute for Evolutionary Biology

Dr. Philipp Rausch

Postdoctoral Researcher, Associated Junior Researcher
Max-Planck-Institute for Evolutionary Biology

Shauni Doms

PhD Candidate
Max-Planck-Institute for Evolutionary Biology Institute for Experimental Medicine

Hanna Fokt

PhD Candidate
Max-Planck-Institute for Evolutionary Biology

Prof. Dr. John Baines

Principal Investigator
Kiel University Institute for Experimental Medicine Max-Planck-Institute for Evolutionary Biology

Publications

2017

The PF4/PPBP/CXCL5 Gene Cluster Is Associated with Periodontitis.

Shusterman A, Munz M, Richter G, Jepsen S, Lieb W, Krone B, Hoffman P, Laudes M, Wellmann J, Berger K, Kocher T, Offenbacher S, Divaris K, Franke A, Schreiber S, Dommisch H, Weiss E, Schaefer A S, Houri-Haddad Y, Iraqi F A (2017); J Dent Res., 1:22034517706311. doi: 10.1177/0022034517706311

A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis.

Munz M, Willenborg C, Richter G M, Jockel-Schneider Y, Graetz C, Staufenbiel I, Wellmann J, Berger K, Krone B, Hoffmann P, Velde N V, Uitterlinden A G, Groot L C P G M, Sawalha A, Direskeneli H, Saruhan-Direskeneli G, Guzeldemir-Akcakanat E, Keceli G, Laudes M, Noack B, Teumer A, Holtfreter B, Kocher T, Eickholz P, Meyle J, Doerfer C, Bruckmann C, Lieb W, Franke A, Schreiber S, Nohutcu R M, Erdmann J, Loos B G, Jepsen S, Dommisch H, Schaefer A (2017); Hum Mol Genet., doi: 10.1093/hmg/ddx151

A post-GWAS analysis of predicted regulatory variants and tuberculosis susceptibility.

Uren C, Henn B M, Franke A, Wittig M, van Helden P D, Hoal E G, Möller M (2017); PLoS One., 12(4):e0174738. doi: 10.1371/journal.pone.0174738

Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample.

Koch M, Freitag-Wolf S, Schlesinger S, Borggrefe J, Hov J R, Jensen M K, Pick J, Markus M R, Höpfner T, Jacobs G, Siegert S, Artati A, Kastenmüller G, Römisch-Margl W, Adamski J, Illig T, Nothnagel M, Karlsen T H, Schreiber S, Franke A, Krawczak M, Nöthlings U, Lieb W (2017); Eur J Clin Nutr., doi: 10.1038/ejcn.2017.43

Genome-wide association analysis for chronic venous disease identifies EFEMP1 and KCNH8 as susceptibility loci.

Ellinghaus E, Ellinghaus D, Krusche P, Greiner A, Schreiber C, Nikolaus S, Gieger C, Strauch K, Lieb W, Rosenstiel P, Frings N, Fiebig A, Schreiber S, Franke A (2017); Sci Rep., 7:45652. doi: 10.1038/srep45652

miRNAs in Ancient Tissue Specimens of the Tyrolean Iceman.

Keller A, Kreis S, Leidinger P, Maixner F, Ludwig N, Backes C, Galata V, Guerriero G, Fehlmann T, Franke A, Meder B, Zink A, Meese E (2017); Mol Biol Evol., 34(4):793-801. doi: 10.1093/molbev/msw291

Inflammatory bowel disease and oral health: systematic review and a meta-analysis.

Papageorgiou S N, Hagner M, Nogueira A V, Franke A, Jäger A, Deschner J (2017); J Clin Periodontol., 44(4):382-393. doi: 10.1111/jcpe.12698

MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing.

Gyvyte U, Juzenas S, Salteniene V, Kupcinskas J, Poskiene L, Kucinskas L, Jarmalaite S, Stuopelyte K, Steponaitiene R, Hemmrich-Stanisak G, Hübenthal M, Link A, Franke S, Franke A, Pangonyte D, Lesauskaite V, Kupcinskas L, Skieceviciene J (2017); Oncotarget., 16664. doi: 10.18632/oncotarget.16664

LitDB – Keeping Track of Research Papers From Your Institute Made Simple.

Bethune J, Kraemer L, Thomsen I, Keller A, Ellinghaus D, Franke A (2017); Source Code Biol Med., 12:5. doi: 10.1186/s13029-017-0065-2

Association mapping of morphological traits in wild and captive zebra finches: reliable within, but not between populations.

Knief U, Schielzeth H, Backström N, Hemmrich-Stanisak G, Wittig M, Franke A, Griffith S C, Ellegren H, Kempenaers B, Forstmeier W (2017); Mol Ecol., 26(5):1285-1305. doi: 10.1111/mec.14009

Opportunities and challenges of whole-genome and -exome sequencing.

Petersen B S, Fredrich B, Hoeppner M P, Ellinghaus D, Franke A (2017); BMC Genet., 18(1):14. doi: 10.1186/s12863-017-0479-5

Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism.

Rühle F, Witten A, Barysenka A, Huge A, Arning A, Heller C, Krümpel A, Mesters R, Franke A, Lieb W, Riemenschneider M, Hiersche M, Limperger V, Nowak-Göttl U, Stoll M (2017); Blood., 129(6):783-790. doi: 10.1182/blood-2016-07-728840

Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

Ji S G, Juran B D, Mucha S, Folseraas T, Jostins L, Melum E […] Rushbrook S M, Franke A, Karlsen T H, Lazaridis K N, Anderson C A (2017); Nat Genet., 49(2):269-273. doi: 10.1038/ng.3745

Inflammatory Bowel Disease: A Global Disease That Needs a Broader Ensemble of Populations.

Franke A (2017); Gastroenterology., 152(1):14-16. doi: 10.1053/j.gastro.2016.11.026

2016

Association Between Loss-of-Function Mutations Within the FANCM Gene and Early-Onset Familial Breast Cancer.

Neidhardt G, Hauke J, Ramser J, Groß E, Gehrig A, Müller C R, Kahlert A K, Hackmann K, Honisch E, Niederacher D, Heilmann-Heimbach S, Franke A, Lieb W, Thiele H, Altmüller J, Nürnberg P, Klaschik K, Ernst C, Ditsch N, Jessen F, Ramirez A, Wappenschmidt B, Engel C, Rhiem K, Meindl A, Schmutzler R K, Hahnen E (2016); JAMA Oncol., doi: 10.1001/jamaoncol.2016.5592

Beneficial Effects of a Dietary Weight Loss Intervention on Human Gut Microbiome Diversity and Metabolism Are Not Sustained during Weight Maintenance.

Heinsen F A, Fangmann D, Müller N, Schulte D M, Rühlemann M C, Türk K, Settgast U, Lieb W, Baines J F, Schreiber S, Franke A, Laudes M (2016); Obes Facts., 9(6):379-391. doi: 10.1159/000449506

Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome.

Henström M, Diekmann L, Bonfiglio F, Hadizadeh F, Kuech E M, von Köckritz-Blickwede M, Thingholm L B, Zheng T, Assadi G, Dierks C, Heine M, Philipp U, Distl O, Money M E, Belheouane M, Heinsen F A, Rafter J, Nardone G9, Cuomo R, Usai-Satta P, Galeazzi F, Neri M, Walter S, Simrén M, Karling P, Ohlsson B, Schmidt P T, Lindberg G, Dlugosz A, Agreus L, Andreasson A, Mayer E, Baines J F, Engstrand L, Portincasa P, Bellini M, Stanghellini V, Barbara G, Chang L, Camilleri M, Franke A, Naim H Y, D’Amato M (2016); Gut., pii:gutjnl-2016-312456. doi: 10.1136/gutjnl-2016-312456

The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota.

Lagkouvardos I, Pukall R, Abt B, Foesel B U, Meier-Kolthoff J P, Kumar N, Bresciani A, Martínez I, Just S, Ziegler C, Brugiroux S, Garzetti D, Wenning M, Bui T P N, Wang J, Hugenholtz F, Plugge C M, Peterson D A, Hornef M W, Baines J F, Smidt H, Walter J, Kristiansen K, Nielsen H B, Haller D, Overmann J, Stecher B, Clavel T (2016);
Nat Microbiol., 1(11):16219. doi: 10.1038/nmicrobiol.2016.219

Rare phenotypes in the understanding of autoimmunity.

Zeissig Y, Petersen B S, Franke A, Blumberg R S, Zeissig S (2016); Immunol Cell Biol., doi: 10.1038/icb.2016.76

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); Nature Genetics. doi: 10.1038/ng.3695

The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation.

Schrumpf E, Kummen M, Valestrand L, Greiner T U, Holm K, Arulampalam V, Reims H M, Baines J, Bäckhed F, Karlsen T H, Blumberg R S, Hov J R, Melum E (2016); J Hepatol., pii: S0168-8278(16)30559-1. doi: 10.1016/j.jhep.2016.09.020

Male-specific association between MT-ND4 11719 A/G polymorphism and ulcerative colitis: a mitochondria-wide genetic association study.

Dankowski T, Schröder T, Möller S, Yu X, Ellinghaus D, Bär F, Fellermann K, Lehnert H, Schreiber S, Franke A, Sina C, Ibrahim S M, König I R (2016); BMC Gastroenterol., 16(1):118. doi: 10.1186/s12876-016-0509-1

Genetic Factors of the Disease Course After Sepsis: Rare Deleterious Variants Are Predictive.

Taudien S, Lausser L, Giamarellos-Bourboulis E J, Sponholz C, Schöneweck F, Felder M, Schirra L R, Schmid F, Gogos C, Groth S, Petersen B S, Franke A, Lieb W, Huse K, Zipfel P F, Kurzai O, Moepps B, Gierschik P, Bauer M, Scherag A, Kestler H A, Platzer M (2016); EBioMedicine., 2:227-238. doi: 10.1016/j.ebiom.2016.08.037

Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease.

Häsler R, Sheibani-Tezerji R, Sinha A, Barann M, Rehman A, Esser D, Aden K, Knecht C, Brandt B, Nikolaus S, Schäuble S, Kaleta C, Franke A, Fretter C, Müller W, Hütt M T, Krawczak M, Schreiber S, Rosenstiel P (2016); Gut, pii: gutjnl-2016-311651. doi: 10.1136/gutjnl-2016-311651

Fitness consequences of polymorphic inversions in the zebra finch genome.

Knief U, Hemmrich-Stanisak G, Wittig M, Franke A, Griffith S C, Kempenaers B, Forstmeier W (2016); Genome Biol., 17(1):199. doi: 10.1186/s13059-016-1056-3

CD4+ T cells from patients with primary sclerosing cholangitis exhibit reduced apoptosis and down-regulation of proapoptotic Bim in peripheral blood.

Schoknecht T, Schwinge D, Stein S, Weiler-Normann C, Sebode M, Mucha S, Otto B, Ellinghaus E, Stahl F, Franke A, Lohse A W, Herkel J, Schramm C (2016); J Leukoc Biol., pii: jlb.5A1015-469R. doi: 10.1189/jlb.5A1015-469R

Paired proteomics, transcriptomics and miRNomics in non-small cell lung cancers: known and novel signaling cascades.

Backes C, Ludwig N, Leidinger P, Huwer H, Tenzer S, Fehlmann T, Franke A, Meese E, Lenhof H P, Keller A (2016); Oncotarget. doi: 10.18632/oncotarget.11723

Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis.

Tschurtschenthaler M, Kachroo P, Heinsen F A, Adolph T E, Rühlemann M C, Klughammer J, Offner F A, Ammerpohl O, Krueger F, Smallwood S, Szymczak S, Kaser A, Franke A (2016); Sci Rep., 6:31640. doi: 10.1038/srep31640

Immunochip analysis identifies association of the RAD50/IL13 region with human longevity.

Flachsbart F, Ellinghaus D, Gentschew L, Heinsen F A, Caliebe A, Christiansen L, Nygaard M, Christensen K, Blanché H, Deleuze JF, Derbois C, Galan P, Büning C, Brand S, Peters A, Strauch K, Müller-Nurasyid M, Hoffmann P, Nöthen MM, Lieb W, Franke A, Schreiber S, Nebel A (2016); Aging Cell, 15(3):585-588. doi: 10.1111/acel.12471

Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis.

Rühlemann MC, Heinsen F A, Zenouzi R, Lieb W, Franke A, Schramm C (2016); Gut, pii:gutjnl-2016-312180. doi: 10.1136/gutjnl-2016-312180

Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B, Park Y R, Raychaudhuri S, Pouget J G , Hübenthal M, Folseraas T, Wang Y, Esko T, Metspalu A, Westra HJ, Franke L, Pers T H, Weersma R K, Collij V, D’Amato M, Halfvarson J, Jensen AB, Lieb W, Degenhardt F, Forstner A J, Hofmann A, Schreiber S, Mrowietz U, Juran B D, Lazaridis K N, Brunak S, Dale AM, Trembath R C, Weidinger S, Weichenthal M, Ellinghaus E, Elder J T, Barker J N, Andreassen O A, McGovern  D P, Karlsen T H, Barrett  J C, Parkes M, Brown M A, Franke A (2016); Nat Gen, 48(5):510-8. doi: 10.1038/ng.3528

Genome-wide association study of serum coenzyme Q10 levels identifies susceptibility loci linked to neuronal diseases.

Degenhardt F, Niklowitz P, Szymczak S, Jacobs G, Lieb W, Menke T, Laudes M, Esko T, Weidinger S, Franke A, Döring F, Onur S (2016); Hum. Mol. Genet., 25(13):2881-2891. doi: 10.1093/hmg/ddw134

Epithelial calcineurin controls microbiota-dependent intestinal tumor development.

Peuker K, Muff S, Wang J, Künzel S, Bosse E, Zeissig Y, Luzzi G, Basic M, Strigli A, Ulbricht A, Kaser A, Arlt A, Chavakis T, van den Brink G R, Schafmayer C, Egberts J H, Becker T, Bianchi M E, Bleich A, Röcken C, Hampe J, Schreiber S, Baines J F, Blumberg R S, Zeissig S (2016); Nat Med., 22(5):506-15. doi: 10.1038/nm.4072

Stool frequency is associated with gut microbiota composition.

Hadizadeh F, Walter S, Belheouane M, Bonfiglio F, Heinsen F A, Andreasson A, Agreus L, Engstrand L, Baines J F, Rafter J, Franke A, D’Amato M (2016); Gut., pii:gutjnl-2016-311935. doi: 10.1136/gutjnl-2016-311935

Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease.

Yokoyama J S, Wang Y, Schork A J, Thompson W K, Karch C M, Cruchaga C, McEvoy L K, Witoelar A, Chen C H, Holland D, Brewer J B, Franke A, Dillon W P, Wilson D M, Mukherjee P, Hess C P, Miller Z, Bonham L W, Shen J, Rabinovici G D, Rosen H J, Miller B L, Hyman B T, Schellenberg G D, Karlsen T H, Andreassen O A, Dale A M, Desikan R S (2016); JAMA Neurol., doi: 10.1001/jamaneurol.2016.0150.

Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations.

Moschen A R, Gerner R R, Wang J, Klepsch V, Adolph T E, Reider S J, Hackl H, Pfister A, Schilling J, Moser P L, Kempster S L, Swidsinski A, Orth Höller D, Weiss G, Baines J F, Kaser A, Tilg H (2016); Cell Host Microbe., 19(4):455-69. doi: 10.1016/j.chom.2016.03.007

1053 Bloom of Fecal Megamonas After a 4 Week High Oral Fructose Challenge Disturbs Energy and Lipid Metabolism: Linking Diet to Microbiota, Bile Acid and Host Metabolism Alterations

Kienbacher C, Traussnigg S, Halilbasic E, Fuchs C D, Dolak W, Munda P, Stojakovic T, Fauler G, Forster M, Heinsen F A, Rühlemann M C, Franke A, Trauner M H (2016); Gastroenterology, 150(4):S1056-S1057. doi: 10.1016/S0016-5085(16)33568-5

Genome-wide rare copy number variation screening in ulcerative colitis identifies potential susceptibility loci.

Saadati H R, Wittig M, Helbig I, Häsler R, Anderson C A, Mathew C G, Kupcinskas L, Parkes M, Karlsen T H, Rosenstiel P, Schreiber S, Franke A (2016); BMC Med. Genet.,  doi: 10.1186/s12881-016-0289-z

Getting the Hologenome Concept Right: An Eco-Evolutionary Framework for Hosts and Their Microbiomes.

Theis K R, Dheilly N M, Klassen J L, Brucker R M, Baines J F, Bosch T C, Cryan J F, Gilbert S F, Goodnight C J, Lloyd E A, Sapp J, Vandenkoornhuyse P, Zilber-Rosenberg I, Rosenberg E, Bordenstein S R (2016); mSystems., 1(2).pii:e00028-16. doi: 10.1128/mSystems.00028-16

Interdisciplinary approach towards a systems medicine toolbox using the example of inflammatory diseases.

Bauer C R, Knecht C, Fretter C, Baum B, Jendrossek S, Rühlemann M, Heinsen F A, Umbach N, Grimbacher B, Franke A, Lieb W, Krawczak M, Hütt MT, Sax U (2016); Brief. Bioinformatics., pii:bbw024. doi: 10.1093/bib/bbw024

Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease.

Stitziel NO, Stirrups KE, Masca NG, Erdmann J, Ferrario PG, König IR, Weeke PE, Webb TR, Auer PL, Schick UM, Lu Y, Zhang H, Dube MP, Goel A, Farrall M, Peloso GM, Won HH, Do R, van Iperen E, Kanoni S, Kruppa J, Mahajan A, Scott RA, Willenborg C, Braund PS, van Capelleveen JC, Doney AS, Donnelly LA, Asselta R, Merlini PA, Duga S, Marziliano N, Denny JC, Shaffer CM, El-Mokhtari NE, Franke A, Gottesman O, Heilmann S, Hengstenberg C, Hoffmann P, Holmen OL, Hveem K, Jansson JH, Jöckel KH, Kessler T, Kriebel J, Laugwitz KL, Marouli E, Martinelli N, McCarthy MI, Van Zuydam NR, Meisinger C, Esko T, Mihailov E, Escher SA, Alver M, Moebus S, Morris AD, Müller-Nurasyid M, Nikpay M, Olivieri O, Perreault LP, AlQarawi A, Robertson NR, Akinsanya KO, Reilly DF, Vogt TF, Yin W, Asselbergs FW, Kooperberg C, Jackson RD, Stahl E, Strauch K, Varga TV, Waldenberger M, Zeng L, Kraja AT, Liu C, Ehret GB, Newton-Cheh C, Chasman DI, Chowdhury R, Ferrario M, Ford I, Jukema J, Kee F, Kuulasmaa K, Nordestgaard BG, Perola M, Saleheen D, Sattar N, Surendran P, Tregouet D, Young R, Howson JM, Butterworth AS, Danesh J, Ardissino D, Bottinger EP, Erbel R, Franks PW, Girelli D, Hall AS, Hovingh G, Kastrati A, Lieb W, Meitinger T, Kraus WE, Shah SH, McPherson R, Orho-Melander M, Melander O, Metspalu A, Palmer CN, Peters A, Rader DJ, Reilly MP, Loos RJ, Reiner AP, Roden DM, Tardif JC, Thompson JR, Wareham NJ, Watkins H, Willer CJ, Kathiresan S, Deloukas P, Samani NJ, Schunkert H (2016); N Engl J Med,, 374:1134-1144. doi: 10.1056/NEJMoa1507652

Integrated quantitative proteomic and transcriptomic analysis of lung tumor and control tissue: a lung cancer showcase.

Tenzer S, Leidinger P, Backes C, Huwer H, Hildebrandt A, Lenhof H P, Wesse T, Franke A, Meese E, Keller A (2016); Oncotarget, 7(12):14857-70. doi: 10.18632/oncotarget.7562.

Multicenter quality assessment of 16S ribosomal DNA-sequencing for microbiome analyses reveals high inter-center variability.

Hiergeist A, Reischl U, Priority Program 1656 Intestinal Microbiota Consortium / quality assessment participants, Gessner A (2016); Int J Med Microbiol., 306(5):334-42. doi: 10.1016/j.ijmm.2016.03.005

Haplotype synthesis analysis reveals functional variants underlying known genome-wide associated susceptibility loci.

Lacour A, Ellinghaus D, Schreiber S, Franke A, Becker T (2016); Bioinformatics., doi: 10.1093/bioinformatics/btw125

Corrigendum: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.

Huang Y H, Zhu C, Kondo Y, Anderson A C, Gandhi A, Russell A, Dougan S K, Petersen BS, Melum E, Pertel T, Clayton K L, Raab M, Chen Q, Beauchemin N, Yazaki P J, Pyzik M, Ostrowski M A, Glickman J N, Rudd C E, Ploegh H L, Franke A, Petsko G A, Kuchroo V K, Blumberg R S (2016); Nature, 517:386-390. doi: 10.1038/nature17421

Analysis of factors contributing to variation in the C57BL/6J fecal microbiota across German animal facilities

Rausch P, Basic M, Batra A, Bischoff S C, Blaut M, Clavel T, Gläsner J, Gopalakrishnan S, Grassl G A, Günther C, Haller D, Hirose M, Ibrahim S, Loh G, Mattner J, Nagel S, Pabst O, Schmidt F, Siegmund B, Strowig T, Volynets V, Wirtz S, Zeissig S, Zeissig Y, Bleich A, Baines J F (2016); Int J Med Microbiol., 306(5):343-55. doi:10.1016/j.ijmm.2016.03.004

The role of tissue-specific microbiota in initial establishment success of Pacific oysters.

Lokmer A, Kuenzel S, Baines, J F, Wegner K M (2016); Environmental Microbiology, 18(3):970-987. doi: 10.1111/1462-2920.13163

Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages.

Schieck M, Schouten J P, Michel S, Suttner K, Toncheva A, Gaertner V D, Illig T, Lipinski S, Franke A, Klintschar M, Kalayci O, Sahiner U M, Birben E, Melén E, Pershagen G, Freidin M B, Ogorodova L M, Granell R, Henderson J, Brunekreef B, Smit H A, Vogelberg C, von Berg A, Bufe A, Heinzmann A, Laub O, Rietschel E, Simma B, Genuneit J, Jonigk D, Postma D S, Koppelman G H, Vonk J M, Timens W, Boezen H M, Kabesch M (2016); J. Allergy Clin. Immunol., doi: 10.1016/j.jaci.2015.12.1305

Dissecting genetics of cutaneous miRNA in a mouse model of an autoimmune blistering disease.

Gupta Y, Möller S, Witte M, Belheouane M, Sezin T, Hirose M, Vorobyev A, Niesar F, Bischof J, Ludwig R J, Zillikens D, Sadik C D, Restle T, Häsler R, Baines J F, Ibrahim S M (2016); BMC Genomics, 17:112. doi: 10.1186/s12864-016-2455-2.

Deep characterization of blood cell miRNomes by NGS.

Schwarz E C, Backes C, Knörck A, Ludwig N, Leidinger P, Hoxha C, Schwär G, Grossmann T, Müller S C, Hart M, Haas J, Galata V, Müller I, Fehlmann T, Eichler H, Franke A, Meder B, Meese E, Hoth M, Keller A (2016); Cell Mol Life Sci, 73(16):3169-81. doi: 10.1007/s00018-016-2154-9

2015

Composition of Bacterial Communities Associated with Aurelia aurita Changes with Compartment, Life Stage, and Population.

Weiland-Bräuer N, Neulinger S C, Pinnow N, Künzel S, Baines J F, Schmitz R A (2015); Appl Environ Microbiol., 81(17):6038-6052.  doi: 10.1128/AEM.01601-15

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin.

Heinsen F A, Knecht H, Neulinger S C, Schmitz R A, Knecht C, Kühbacher T, Rosenstiel P C, Schreiber S, Friedrichs A K, Ott S J (2015); Gut Microbes., 6(4):243-54. doi: 10.1080/19490976.2015.1062959.

Vy-PER: eliminating false positive detection of virus integration events in next generation sequencing data.

Forster M, Szymczak S, Ellinghaus D, Hemmrich G, Rühlemann M, Kraemer L, Mucha S, Wienbrandt L, Stanulla M; UFO Sequencing Consortium within I-BFM Study Group, Franke A (2015); Sci Rep., 5:11534. doi: 10.1038/srep11534.

Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection.

Rausch P, Steck N, Suwandi A, Seidel J A, Künzel S, Bhullar K, Basic M, Bleich A, Johnsen J M, Vallance B A, Baines J F, Grassl G A (2015); PLoS Pathog, 11(7):e1005008. doi: 10.1371/journal.ppat.1005008

Analysis of intestinal microbiota in hybrid house mice reveals evolutionary divergence in a vertebrate hologenome.

Wang J, Kalyan S, Steck N, Turner L M, Harr B, Künzel S, Vallier M, Häsler R, Franke A, Oberg H-H, Ibrahim S M, Grassl G A, Kabelitz D, Baines J F (2015); Nature Commun., 6:6440. doi: 10.1038/ncomms7440

Development of a high-resolution NGS-based HLA-typing and analysis pipeline.

Wittig M, Anmarkrud J A, Kässens J C, Koch S, Forster M, Ellinghaus E, Hov J R, Sauer S, Schimmler M, Ziemann M, Görg S, Jacob F, Karlsen T H, Franke A (2015); Nucleic Acids Res., 43(11):e70. doi: 10.1093/nar/gkv184

High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis.

Goyette, P, Boucher G, Mallon D, Ellinghaus E, Jostins L, Huang H, […], Franke A, Rioux J D (2015); Nature Genetics, 47:172-179. doi: 10.1038/ng.3176

Geographical patterns of the standing and active human gut microbiome in health and IBD.

Rehman A, Rausch P, Wang J, Skieceviciene J, Kiudelis G, Bhagalia K, Amarapurkar D, Kupcinskas L, Schreiber S, Rosenstiel P, Baines J F, Ott S (2015); Gut, 65(2):238-248. doi: 10.1136/gutjnl-2014-308341

2014

Early-onset Crohn’s disease and autoimmunity associated with a variant in CTLA-4.

Zeissig S, Petersen B S, Tomczak M, Melum E, Huc-Claustre E, Dougan S K, Laerdahl J K, Stade B, Forster M, Schreiber S, Weir D, Leichtner A M, Franke A, Blumberg R S (2015); Gut., 64(12):1889-97. doi: 10.1136/gutjnl-2014-308541

GrabBlur–a framework to facilitate the secure exchange of whole-exome and -genome SNV data using VCF files.

Stade B, Seelow D, Thomsen I, Krawczak M, Franke A (2014); BMC Genomics., 4:S8. doi: 10.1186/1471-2164-15-S4-S8

Whole genome and exome sequencing of monozygotic twins discordant for Crohn’s disease.

Petersen B S, Spehlmann M E, Raedler A, Stade B, Thomsen I, Rabionet R, Rosenstiel P, Schreiber S, Franke A (2014); BMC Genomics, 15(1):564. doi: 10.1186/1471-2164-15-564

Type I interferon signalling in the intestinal epithelium affects Paneth cells, microbial ecology and epithelial regeneration

Tschurtschenthaler M, Wang J, Fricke C, Fritz T M, Niederreiter L, Adolph T E, Sarcevic E, Künzel S, Offner F A, Kalinke U, Baines J F, Tilg H, Kaser A (2014); Gut., 63(12):1921-31. doi: 10.1136/gutjnl-2013-305863

Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age.

Deelen J, Beekman M, Uh H W, Broer L, Ayers K L, Tan Q, Kamatani Y, Bennet A M, Tamm R, Trompet S, Guðbjartsson D F, Flachsbart F, Rose G, Viktorin A, Fischer K, Nygaard M, Cordell H J, Crocco P, van den Akker E B, Böhringer S, Helmer Q, Nelson C P, Saunders G I, Alver M, Andersen-Ranberg K, Breen M E, van der Breggen R, Caliebe A, Capri M, Cevenini E, Collerton J C, Dato S, Davies K, Ford I, Gampe J, Garagnani P, de Geus E J, Harrow J, van Heemst D, Heijmans B T, Heinsen F A, Hottenga J J, Hofman A, Jeune B, Jonsson P V, Lathrop M, Lechner D, Martin-Ruiz C, Mcnerlan S E, Mihailov E, Montesanto A, Mooijaart S P, Murphy A, Nohr E A, Paternoster L, Postmus I, Rivadeneira F, Ross O A, Salvioli S, Sattar N, Schreiber S, Stefánsson H, Stott D J, Tiemeier H, Uitterlinden A G, Westendorp RG, Willemsen G, Samani N J, Galan P, Sørensen T I, Boomsma D I, Jukema J W, Rea I M, Passarino G, de Craen A J, Christensen K, Nebel A, Stefánsson K, Metspalu A, Magnusson P, Blanché H, Christiansen L, Kirkwood T B, van Duijn C M, Franceschi C, Houwing-Duistermaat J J, Slagboom P E (2014); Hum Mol Genet., 23(16):4420-32. doi: 10.1093/hmg/ddu139

Dietary history contributes to enterotype-like clustering and functional metagenomic content in the intestinal microbiome of wild mice.

Wang J, Linnenbrink M, Künzel S, Fernandes R, Nadeau M J, Rosenstiel P, Baines J F (2014); Proc Natl Acad Sci U S A., 111(26):E2703-10. doi: 10.1073/pnas.1402342111

Effects of β-lactam antibiotics and fluoroquinolones on human gut microbiota in relation to Clostridium difficile associated diarrhea.

Knecht H, Neulinger S C, Heinsen F A, Knecht C, Schilhabel A, Schmitz R A, Zimmermann A, dos Santos V M, Ferrer M, Rosenstiel P C, Schreiber S, Friedrichs A K, Ott S J (2014); PLoS One., 9(2):e89417. doi: 10.1371/journal.pone.0089417

XIAP variants in male Crohn’s disease.

Zeissig Y, Petersen B S, Milutinovic S, Bosse E, Mayr G, Peuker K, Hartwig J, Keller A, Kohl M, Laass M W, Billmann-Born S, Brandau H, Feller A C, Röcken C, Schrappe M, Rosenstiel P, Reed J C, Schreiber S, Franke A, Zeissig S (2014); Gut., 64(1):66-76. doi: 10.1136/gutjnl-2013-306520

Investigation of complement component C4 copy number variation in human longevity.

Flachsbart F, Caliebe A, Heinsen F A, Hemming-Karlsen T, Schreiber S, Franke A, Nebel A (2014); PLoS One., 9(1):e86188. doi: 10.1371/journal.pone.0086188

2013

Bacterial colonization of Hydra hatchlings follows a robust temporal pattern.

Franzenburg S, Fraune S, Altrock P M, Künzel S, Baines J F, Traulsen A, Bosch T C G (2013); ISME J., 7(4):781-90. doi: 10.1038/ismej.2012.156

Genome-wide mapping of gene-microbiota interactions in susceptibility to autoimmune skin blistering.

Srinivas G, Möller S, Wang J, Künzel S, Zillikens D, Baines J F, Ibrahim S M (2013); Nature Commun., 4:2462. doi: 10.1038/ncomms3462

Distinct antimicrobial peptide expression determines host species-specific bacterial associations

Franzenburg S, Walter J, Künzel S, Wang J, Baines J F, Bosch T C G, Fraune S (2013); Proc Natl Acad Sci USA, 110(39):E3730-8. doi: 10.1073/pnas.1304960110

Gut microbiota disturbance during antibiotic therapy: a multi-omic approach.

Pérez-Cobas A E, Gosalbes M J, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, Neulinger S C, Däumer C, Heinsen F A, Latorre A, Barbas C, Seifert J, dos Santos V M, Ott S J, Ferrer M, Moya A (2013); Gut., 62(11):1591-601. doi: 10.1136/gutjnl-2012-303184

Non-invasive analysis of microbiome
 dynamics in the fruit fly Drosophila melanogaster.

Fink C, Staubach F, Kuenzel S, Baines JF, Roeder T (2013); Appl Environ Microbiol., 79(22):6984-6988. doi: 10.1128/AEM.01903-13

Association between variants of PRDM1 and NDP52 and Crohn’s disease, based on exome sequencing and functional studies.

Ellinghaus D, Zhang H, Zeissig S, Lipinski S, Till A, Jiang T, Stade B, Bromberg Y, Ellinghaus E, Keller A, Rivas M A, Skieceviciene J, Doncheva N T, Liu X, Liu Q, Jiang F, Forster M, Mayr G, Albrecht M, Häsler R, Boehm B O, Goodall J, Berzuini C R, Lee J, Andersen V, Vogel U, Kupcinskas L, Kayser M, Krawczak M, Nikolaus S, Weersma R K, Ponsioen C Y, Sans M, Wijmenga C, Strachan D P, McArdle W L, Vermeire S, Rutgeerts P, Sanderson J D, Mathew C G, Vatn M H, Wang J, Nöthen M M, Duerr R H, Büning C, Brand S, Glas J, Winkelmann J, Illig T, Latiano A, Annese V, Halfvarson J, D’Amato M, Daly M J, Nothnagel M, Karlsen T H, Subramani S, Rosenstiel P, Schreiber S, Parkes M, Franke A (2013); Gastroenterology., 145(2):339-47. doi: 10.1053/j.gastro.2013.04.040

Base-pair resolution DNA methylome of the EBV-positive Endemic Burkitt lymphoma cell line DAUDI determined by SOLiD bisulfite-sequencing.

Kreck B, Richter J, Ammerpohl O, Barann M, Esser D, Petersen B S, Vater I, Murga Penas E M, Bormann Chung C A, Seisenberger S, Lee Boyd V, Smallwood S, Drexler H G, Macleod R A, Hummel M, Krueger F, Häsler R, Schreiber S, Rosenstiel P, Franke A, Siebert R (2013); Leukemia., 27(8):1751-3. doi: 10.1038/leu.2013.4

The role of biogeography in shaping diversity of the intestinal microbiota in house mice.

Linnenbrink M, Wang J, Hardouin E A, Künzel S, Metzler D, Baines J F (2013); Mol Ecol., 22(7):1904-16. doi: 10.1111/mec.12206

2012

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

Jostins L, Ripke S, Weersma RK, Duerr R H, McGovern D P, Hui K Y, Lee J C, Schumm L P, Sharma Y, Anderson C A, Essers J, […], Mathew C G, Rioux J D, Schadt E E, Daly M J, Franke A, […] (2012); Nature., 491(7422):119-24. doi: 10.1038/nature11582

MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers.

Franzenburg S, Fraune S, Künzel S, Baines J F, Domazet-Loso T, Bosch T C G (2012); Proc Natl Acad Sci USA, 109(47):19374-9. doi: 10.1073/pnas.1213110109

MyD88 deficient Hydra reveal an ancient function of TLR-signaling in sensing bacterial colonizers.

Franzenburg S, Fraune S, Künzel S, Baines J F, Domazet-Loso T, Bosch T C (2012); Proc Natl Acad Sci U S A., 109(47):19374-9. doi: 10.1073/pnas.1213110109

Expression of the blood-group-related glycosyltransferase B4galnt2 influences the intestinal microbiota in mice.

Staubach F, Künzel S, Baines A C, Yee A, McGee B M, Bäckhed F, Baines J F, Johnsen J M (2012); ISME J., 6(7):1345-55. doi: 10.1038/ismej.2011.204

Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.

Ellinghaus E, Stanulla M, Richter G, Ellinghaus D, te Kronnie G, Cario G, Cazzaniga G, Horstmann M, Panzer Grümayer R, Cavé H, Trka J, Cinek O, Teigler-Schlegel A, ElSharawy A, Häsler R, Nebel A, Meissner B, Bartram T, Lescai F, Franceschi C, Giordan M, Nürnberg P, Heinzow B, Zimmermann M, Schreiber S, Schrappe M, Franke A (2012); Leukemia., 26(5):902-9. doi: 10.1038/leu.2011.302

Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci.

Folseraas T, Melum E, Rausch P, Juran B D, Ellinghaus E, Shiryaev A, Laerdahl J K, Ellinghaus D, Schramm C, Weismüller T J, Gotthardt D N, Hov J R, Clausen O P, Weersma R K, Janse M, Boberg K M, Björnsson E, Marschall H U, Cleynen I, Rosenstiel P, Holm K, Teufel A, Rust C, Gieger C, Wichmann H E, Bergquist A, Ryu E, Ponsioen C Y, Runz H, Sterneck M, Vermeire S, Beuers U, Wijmenga C, Schrumpf E, Manns M P, Lazaridis K N, Schreiber S, Baines J F, Franke A, Karlsen T H (2012); J Hepatol., 57(2):366-75. doi: 10.1016/j.jhep.2012.03.031

Microbial exposure during early life has persistent effects on natural killer T cell function.

Olszak T, An D, Zeissig S, Vera M P, Richter J, Franke A, Glickman J N, Siebert R, Baron R M, Kasper D L, Blumberg R S (2012); Science., 336(6080):489-93. doi: 10.1126/science.1219328

Effects of probiotics and antibiotics on the intestinal homeostasis in a computer controlled model of the large intestine.

Rehman A, Heinsen F A, Koenen M E, Venema K, Knecht H, Hellmig S, Schreiber S, Ott S J (2012);
BMC Microbiol., 12:47. doi: 10.1186/1471-2180-12-47

2011

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype

Rausch P, Rehman A, Künzel S, Häsler R, Ott S J, Schreiber S, Rosenstiel P, Franke A, Baines J F (2011); Proc Natl Acad Sci USA, 108 (47): 19030-5. doi: 10.1073/pnas.1106408108

Long-term balancing selection at the blood group-related gene B4galnt2 in the genus Mus (Rodentia; Muridae)

Linnenbrink M, Johnsen J M, Montero I, Brzezinski C R, Harr B, Baines J F (2011); Mol Biol Evol, 28 (11):2999-3003. doi: 10.1093/molbev/msr150

A genome-wide association study reveals evidence of association with sarcoidosis at 6p12.1.

Hofmann S, Fischer A, Till A, Müller-Quernheim J, Häsler R, Franke A, Gäde K I, Schaarschmidt H, Rosenstiel P, Nebel A, Schürmann M, Nothnagel M, Schreiber S; GenPhenReSa Consortium (2011); Eur Respir J., 38(5):1127-35. doi: 10.1183/09031936.00001711

Nod2 is essential
 for temporal development of intestinal microbial communities.

Rehman A, Sina C, Gavrilova O, Häsler R, Ott S, Baines J F, Schreiber S, Rosenstiel P (2011); Gut, 60(10):1354-62. doi: 10.1136/gut.2010.216259

A tissue-specific landscape of sense/antisense transcription in the mouse intestine.

Klostermeier U C, Barann M, Wittig M, Häsler R, Franke A, Gavrilova O, Kreck B, Sina C, Schilhabel M B, Schreiber S, Rosenstiel P (2011); BMC Genomics., 12:305. doi: 10.1186/1471-2164-12-305

2010

Genome-wide metaanalysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci.

Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, Anderson CA, Bis JC, Bumpstead S, Ellinghaus D, Festen EM, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew CG, Montgomery GW, Prescott NJ, Raychaudhuri S, Rotter JI, Schumm P, Sharma Y, Simms LA, Taylor KD, Whiteman D, Wijmenga C, Baldassano RN, Barclay M, Bayless TM, Brand S, Büning C, Cohen A, Colombel JF, Cottone M, Stronati L, Denson T, De Vos M, D’Inca R, Dubinsky M, Edwards C, Florin T, Franchimont D, Gearry R, Glas J, Van Gossum A, Guthery SL, Halfvarson J, Verspaget HW, Hugot JP, Karban A, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, Mowat C, Newman W, Panés J, Phillips A, Proctor DD, Regueiro M, Russell R, Rutgeerts P, Sanderson J, Sans M, Seibold F, Steinhart AH, Stokkers PC, Torkvist L, Kullak-Ublick G, Wilson D, Walters T, Targan SR, Brant SR, Rioux JD, D’Amato M, Weersma RK, Kugathasan S, Griffiths AM, Mansfield JC, Vermeire S, Duerr RH, Silverberg MS, Satsangi J, Schreiber S, Cho JH, Annese V, Hakonarson H, Daly MJ, Parkes M (2010); Nature Genet, 42(12):1118-25. doi: 10.1038/ng.717

Major histocompatibility complex variation and age-specific endoparasite load in subadult European rabbits

Oppelt C, Starkloff A, Rausch P, Von Holst D, Rödel H G (2010); Mol Ecol., 19(19):4155-4167. doi: 10.1111/j.1365-294X.2010.04766.x

Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL).

Franke A, Balschun T, Sina C, Ellinghaus D, Häsler R, Mayr G, Albrecht M, Wittig M, Buchert E, Nikolaus S, Gieger C, Wichmann H E, Sventoraityte J, Kupcinskas L, Onnie CM, Gazouli M, Anagnou N P, Strachan D, McArdle W L, Mathew C G, Rutgeerts P, Vermeire S, Vatn M H; IBSEN study group, Krawczak M, Rosenstiel P, Karlsen T H, Schreiber S (2010); Nat Genet., 42(4):292-4. doi: 10.1038/ng.553

The dynamic genome of Hydra.

Chapman J A, Kirkness E F, Simakov O, Hampson S E, Mitros T, Weinmaier T, Rattei T, Balasubramanian P G, Borman J, Busam D, Disbennett K, Pfannkoch C, Sumin N, Sutton G G, Viswanathan L D, Walenz B, Goodstein D M, Hellsten U, Kawashima T, Prochnik S E, Putnam N H, Shu S, Blumberg B, Dana C E, Gee L, Kibler D F, Law L, Lindgens D, Martinez D E, Peng J, Wigge P A, Bertulat B, Guder C, Nakamura Y, Ozbek S, Watanabe H, Khalturin K, Hemmrich G, Franke A, Augustin R, Fraune S, Hayakawa E, Hayakawa S, Hirose M, Hwang J S, Ikeo K, Nishimiya-Fujisawa C, Ogura A, Takahashi T, Steinmetz P R, Zhang X, Aufschnaiter R, Eder M K, Gorny A K, Salvenmoser W, Heimberg A M, Wheeler B M, Peterson K J, Böttger A, Tischler P, Wolf A, Gojobori T, Remington K A, Strausberg R L, Venter J C, Technau U, Hobmayer B, Bosch T C G, Holstein T W, Fujisawa T, Bode H R, David C N, Rokhsar D S, Steele R E (2010); Nature, 464:592-6. doi: 10.1038/nature08830

2009

G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation.

Sina C, Gavrilova O, Förster M, Till A, Derer S, Hildebrand F, Raabe B, Chalaris A, Scheller J, Rehmann A, Franke A, Ott S, Häsler R, Nikolaus S, Fölsch UR, Rose-John S, Jiang HP, Li J, Schreiber S, Rosenstiel P (2009); J Immunol., 183(11):7514-22. doi: 10.4049/jimmunol.0900063

A functional EXO1 promoter variant is associated with prolonged life expectancy in centenarians.

Nebel A, Flachsbart F, Till A, Caliebe A, Blanché H, Arlt A, Häsler R, Jacobs G, Kleindorp R, Franke A, Shen B, Nikolaus S, Krawczak M, Rosenstiel P, Schreiber S (2009); Mech Ageing Dev., 130(10):691-9. doi: 10.1016/j.mad.2009.08.004

2007

Systematic association mapping identifies NELL1 as a novel IBD disease gene.

Franke A, Hampe J, Rosenstiel P, Becker C, Wagner F, Häsler R, Little R D, Huse K, Ruether A, Balschun T, Wittig M, Elsharawy A, Mayr G, Albrecht M, Prescott N J, Onnie C M, Fournier H, Keith T, Radelof U, Platzer M, Mathew C G, Stoll M, Krawczak M, Nürnberg P, Schreiber S (2007); PLoS One., 2(8):e691. doi: 10.1371/journal.pone.0000691

A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1.

Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht M, Mayr G, De La Vega F M, Briggs J, Günther S, Prescott N J, Onnie C M, Häsler R, Sipos B, Fölsch U R, Lengauer T, Platzer M, Mathew C G, Krawczak M, Schreiber S (2007); Nat Genet., 39(2):207-11. doi: 10.1038/ng1954