{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:46:34Z","timestamp":1792118794767,"version":"4.4.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2012,7,25]],"date-time":"2012-07-25T00:00:00Z","timestamp":1343174400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0041594","type":"journal-article","created":{"date-parts":[[2012,7,25]],"date-time":"2012-07-25T21:19:28Z","timestamp":1343251168000},"page":"e41594","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":194,"title":["Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn\u2019s Disease"],"prefix":"10.1371","volume":"7","author":[{"given":"Melanie","family":"Craven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Egan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scot E.","family":"Dowd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"McDonough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belgin","family":"Dogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Y.","family":"Denkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight","family":"Bowman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen J.","family":"Scherl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,7,25]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1056\/NEJMra0804647","article-title":"Inflammatory bowel disease.","volume":"361(21)","author":"C Abraham","year":"2009","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/01.MIB.0000195385.19268.68","article-title":"Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities.","volume":"12","author":"SB Hanauer","year":"2006","journal-title":"Inflamm Bowel Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease.","volume":"448(7152)","author":"RJ Xavier","year":"2007","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1053\/j.gastro.2007.11.059","article-title":"Microbial influences in inflammatory bowel diseases.","volume":"134(2)","author":"RB Sartor","year":"2008","journal-title":"Gastroenterology"},{"key":"ref5","doi-asserted-by":"crossref","DOI":"10.1038\/ajg.2009.15","article-title":"Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD?","author":"S Singh","year":"2009"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev-genom-082908-150013","article-title":"The genetics of crohn\u2019s disease.","volume":"10","author":"J Van Limbergen","year":"2009","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/QCO.0b013e32832a8a5d","article-title":"Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases.","volume":"22(3)","author":"CD Packey","year":"2009","journal-title":"Curr Opin Infect Dis"},{"key":"ref8","first-page":"339","article-title":"Environmental risk factors for inflammatory bowel disease.","volume":"6(5)","author":"NA Molodecky","year":"2010","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1038\/ajg.2010.140","article-title":"A prospective population-based study of triggers of symptomatic flares in IBD.","volume":"105(9)","author":"CN Bernstein","year":"2010","journal-title":"Am J Gastroenterol"},{"key":"ref10","article-title":"Gastrointestinal infection as a trigger for inflammatory bowel disease.","author":"EA Mann","year":"2011"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1111\/j.1572-0241.2004.40304.x","article-title":"Differential effects of NOD2 variants on crohn\u2019s disease risk and phenotype in diverse populations: A metaanalysis.","volume":"99(12)","author":"M Economou","year":"2004","journal-title":"Am J Gastroenterol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1074\/jbc.C200673200","article-title":"Host recognition of bacterial muramyl dipeptide mediated through NOD2. implications for crohn\u2019s disease.","volume":"278(8)","author":"N Inohara","year":"2003","journal-title":"J Biol Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1126\/science.1103685","article-title":"Nod2 mutation in crohn\u2019s disease potentiates NF-kappaB activity and IL-1beta processing.","volume":"307(5710)","author":"S Maeda","year":"2005","journal-title":"Science"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.immuni.2005.06.004","article-title":"NOD2 and crohn\u2019s disease: Loss or gain of function?","volume":"22(6)","author":"L Eckmann","year":"2005","journal-title":"Immunity"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e10915","DOI":"10.1371\/journal.pone.0010915","article-title":"Direct bacterial killing in vitro by recombinant Nod2 is compromised by crohn\u2019s disease-associated mutations.","volume":"5(6)","author":"LH Perez","year":"2010","journal-title":"PLoS One"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"649","DOI":"10.4161\/auto.5075","article-title":"Genome-wide association scanning highlights two autophagy genes, ATG16L1 and IRGM, as being significantly associated with crohn\u2019s disease.","volume":"3(6)","author":"DC Massey","year":"2007","journal-title":"Autophagy"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/ibd.20512","article-title":"Contributions of IBD5, IL23R, ATG16L1, and NOD2 to crohn\u2019s disease risk in a population-based case-control study: Evidence of gene-gene interactions.","volume":"14(11)","author":"T Okazaki","year":"2008","journal-title":"Inflamm Bowel Dis"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/gast.2002.30294","article-title":"Mucosal flora in inflammatory bowel disease.","volume":"122(1)","author":"A Swidsinski","year":"2002","journal-title":"Gastroenterology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/0140-6736(91)90663-A","article-title":"Effect of faecal stream diversion on recurrence of crohn\u2019s disease in the neoterminal ileum.","volume":"338(8770)","author":"P Rutgeerts","year":"1991","journal-title":"Lancet"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/ismej.2007.52","article-title":"Culture independent analysis of ileal mucosa reveals a selective increase in invasive escherichia coli of novel phylogeny relative to depletion of clostridiales in crohn\u2019s disease involving the ileum.","volume":"1(5)","author":"M Baumgart","year":"2007","journal-title":"ISME J"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0016-5085(98)70019-8","article-title":"Presence of adherent escherichia coli strains in ileal mucosa of patients with crohn\u2019s disease.","volume":"115(6)","author":"A Darfeuille-Michaud","year":"1998","journal-title":"Gastroenterology"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/ibd.20860","article-title":"Molecular diversity of escherichia coli in the human gut: New ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in crohn\u2019s disease.","volume":"15(6)","author":"M Martinez-Medina","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/MOG.0b013e3280105a38","article-title":"Adherent-invasive escherichia coli and crohn\u2019s disease.","volume":"23(1)","author":"N Barnich","year":"2007","journal-title":"Curr Opin Gastroenterol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1462-5822.2009.01381.x","article-title":"Crohn\u2019s disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly.","volume":"12(1)","author":"P Lapaquette","year":"2010","journal-title":"Cell Microbiol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/j.1462-5822.2006.00868.x","article-title":"Adherent-invasive escherichia coli isolated from crohn\u2019s disease patients induce granulomas in vitro.","volume":"9(5)","author":"S Meconi","year":"2007","journal-title":"Cell Microbiol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1086\/338006","article-title":"Oral infection of C57BL\/6 mice with toxoplasma gondii: A new model of inflammatory bowel disease?","volume":"185","author":"O Liesenfeld","year":"2002","journal-title":"J Infect Dis"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1136\/gut.2006.104497","article-title":"Exacerbation of murine ileitis by toll-like receptor 4 mediated sensing of lipopolysaccharide from commensal escherichia coli.","volume":"56(7)","author":"MM Heimesaat","year":"2007","journal-title":"Gut"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"8785","DOI":"10.4049\/jimmunol.177.12.8785","article-title":"Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with toxoplasma gondii.","volume":"177(12)","author":"MM Heimesaat","year":"2006","journal-title":"J Immunol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1136\/gut.23.6.498","article-title":"Features of small intestinal pathology (epithelial cell kinetics, intraepithelial lymphocytes, disaccharidases) in a primary Giardia muris infection.","volume":"23(6)","author":"J Gillon","year":"1982","journal-title":"Gut"},{"key":"ref30","first-page":"3536","article-title":"Infect Immun","volume":"72(6)","year":"2004"},{"key":"ref31","first-page":"181","article-title":"Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut.","volume":"57(2)","author":"T Watanabe","year":"2008"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.anaerobe.2010.06.008","article-title":"Pyrosequencing study of fecal microflora of autistic and control children.","volume":"16(4)","author":"SM Finegold","year":"2010","journal-title":"Anaerobe"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2174\/1874285801004010008","article-title":"A comparison of bacterial composition in diabetic ulcers and contralateral intact skin.","volume":"4","author":"V Gontcharova","year":"2010","journal-title":"Open Microbiol J"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/1471-2180-9-210","article-title":"The effect of the macrolide antibiotic tylosin on microbial diversity in the canine small intestine as demonstrated by massive parallel 16S rRNA gene sequencing.","volume":"9","author":"JS Suchodolski","year":"2009","journal-title":"BMC Microbiol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1128\/IAI.00067-06","article-title":"Adherent and invasive escherichia coli is associated with granulomatous colitis in boxer dogs.","volume":"74(8)","author":"KW Simpson","year":"2006","journal-title":"Infect Immun"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1128\/JCM.42.6.2566-2572.2004","article-title":"Quantification of intestinal bacterial populations by real-time PCR with a universal primer set and minor groove binder probes: A global approach to the enteric flora.","volume":"42(6)","author":"SJ Ott","year":"2004","journal-title":"J Clin Microbiol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1079\/AHRR200131","article-title":"Identification of virulence attributes of gastrointestinal escherichia coli isolates of veterinary significance.","volume":"2(2)","author":"C DebRoy","year":"2001","journal-title":"Anim Health Res Rev"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1574-6968.2000.tb08973.x","article-title":"The yersinia high-pathogenicity island is present in different members of the family enterobacteriaceae.","volume":"183(2)","author":"S Bach","year":"2000","journal-title":"FEMS Microbiol Lett"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1099\/mic.0.27809-0","article-title":"ibeA, a virulence factor of avian pathogenic escherichia coli.","volume":"4)","author":"P Germon","year":"2005","journal-title":"Microbiology 151(Pt"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1086\/315217","article-title":"Extended virulence genotypes of escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise.","volume":"181(1)","author":"JR Johnson","year":"2000","journal-title":"J Infect Dis"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/mi.2009.105","article-title":"CCR2-dependent intraepithelial lymphocytes mediate inflammatory gut pathology during toxoplasma gondii infection.","volume":"2(6)","author":"CE Egan","year":"2009","journal-title":"Mucosal Immunol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/MOG.0b013e3283043596","article-title":"Biologic therapy in crohn\u2019s disease: State of the art.","volume":"24(4)","author":"J Jones","year":"2008","journal-title":"Curr Opin Gastroenterol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"13780","DOI":"10.1073\/pnas.0706625104","article-title":"Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases.","volume":"104(34)","author":"DN Frank","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.3748\/wjg.v11.i8.1131","article-title":"Spatial organization of bacterial flora in normal and inflamed intestine: A fluorescence in situ hybridization study in mice.","volume":"11(8)","author":"A Swidsinski","year":"2005","journal-title":"World J Gastroenterol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/ibd.20783","article-title":"Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal crohn\u2019s disease.","volume":"15(5)","author":"B Willing","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.coph.2010.05.007","article-title":"Animal models of IBD: Linkage to human disease.","volume":"10(5)","author":"A Mizoguchi","year":"2010","journal-title":"Curr Opin Pharmacol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S1542-3565(05)00980-8","article-title":"Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease.","volume":"4(2)","author":"K Takeuchi","year":"2006","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1111\/j.1572-0241.2000.02262.x","article-title":"Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: A case-control study.","volume":"95(8)","author":"JB Felder","year":"2000","journal-title":"Am J Gastroenterol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1440-1746.2008.05772.x","article-title":"Defensins and inflammation: The role of defensins in inflammatory bowel disease.","volume":"24(2)","author":"M Ramasundara","year":"2009","journal-title":"J Gastroenterol Hepatol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1053\/j.gastro.2004.04.061","article-title":"High prevalence of adherent-invasive escherichia coli associated with ileal mucosa in crohn\u2019s disease.","volume":"127(2)","author":"A Darfeuille-Michaud","year":"2004","journal-title":"Gastroenterology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1128\/JB.00233-07","article-title":"The oxidoreductase DsbA plays a key role in the ability of the crohn\u2019s disease-associated adherent-invasive escherichia coli strain LF82 to resist macrophage killing.","volume":"189(13)","author":"MA Bringer","year":"2007","journal-title":"J Bacteriol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1172\/JCI30504","article-title":"CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in crohn disease.","volume":"117(6)","author":"N Barnich","year":"2007","journal-title":"J Clin Invest"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1136\/gut.2010.207456","article-title":"Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive escherichia coli invasion.","volume":"59(10)","author":"N Rolhion","year":"2010","journal-title":"Gut"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"15813","DOI":"10.1073\/pnas.0907722106","article-title":"Nod2 is required for the regulation of commensal microbiota in the intestine.","volume":"106(37)","author":"T Petnicki-Ocwieja","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1053\/gast.2002.32413","article-title":"The molecular classification of the clinical manifestations of crohn\u2019s disease.","volume":"122(4)","author":"T Ahmad","year":"2002","journal-title":"Gastroenterology"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/ismej.2008.37","article-title":"Molecular analysis of the gut microbiota of identical twins with crohn\u2019s disease.","volume":"2(7)","author":"J Dicksved","year":"2008","journal-title":"ISME J"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1136\/gut.2003.028225","article-title":"CCR2 expressing CD4+ T lymphocytes are preferentially recruited to the ileum in crohn\u2019s disease.","volume":"53(9)","author":"SJ Connor","year":"2004","journal-title":"Gut"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.175","article-title":"Genome-wide association defines more than 30 distinct susceptibility loci for crohn\u2019s disease.","volume":"40(8)","author":"JC Barrett","year":"2008","journal-title":"Nat Genet"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1038\/ajg.2010.4","article-title":"The -A2518G polymorphism of monocyte chemoattractant protein-1 is associated with crohn\u2019s disease.","volume":"105(7)","author":"O Palmieri","year":"2010","journal-title":"Am J Gastroenterol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1172\/JCI24335","article-title":"CCR2 modulates inflammatory and metabolic effects of high-fat feeding.","volume":"116(1)","author":"SP Weisberg","year":"2006","journal-title":"J Clin Invest"},{"key":"ref61","first-page":"411","article-title":"Lab Invest.","volume":"92(3)","author":"MA Bringer","year":"2012"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0041594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T23:15:29Z","timestamp":1588979729000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0041594"}},"subtitle":[],"editor":[{"given":"Markus M.","family":"Heimesaat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,7,25]]},"references-count":61,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2012,7,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0041594","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,25]]}}}