{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:55:04Z","timestamp":1791251704725,"version":"4.1.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T00:00:00Z","timestamp":1470787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0160458","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T17:40:20Z","timestamp":1470850820000},"page":"e0160458","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates"],"prefix":"10.1371","volume":"11","author":[{"given":"Sitara S. R.","family":"Ajjampur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Wen","family":"Png","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Ni","family":"Chia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S. W.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,8,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/MOG.0000000000000135","article-title":"The intestinal protozoa: emerging impact on global health and development","volume":"31","author":"JA Turkeltaub","year":"2015","journal-title":"Curr Opin Gastroenterol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.actatropica.2012.12.011","article-title":"Variable geographic distribution of Blastocystis subtypes and its potential implications","volume":"126","author":"MA Alfellani","year":"2013","journal-title":"Acta Trop"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"e0004496","DOI":"10.1371\/journal.pntd.0004496","article-title":"Prevalence and Risk Factors for Intestinal Protozoan Infections with Cryptosporidium, Giardia, Blastocystis and Dientamoeba among Schoolchildren in Tripoli, Lebanon","volume":"10","author":"M Osman","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/1471-2334-14-164","article-title":"Children of Senegal River Basin show the highest prevalence of Blastocystis sp. ever observed worldwide","volume":"14","author":"D El Safadi","year":"2014","journal-title":"BMC Infect Dis"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1756-3305-6-40","article-title":"Blastocystis infection in Malaysia: evidence of waterborne and human-to-human transmissions among the Proto-Malay, Negrito and Senoi tribes of Orang Asli","volume":"6","author":"TS Anuar","year":"2013","journal-title":"Parasit Vectors"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1017\/S0031182012000340","article-title":"Drinking water is a significant predictor of Blastocystis infection among rural Malaysian primary schoolchildren","volume":"139","author":"AM Abdulsalam","year":"2012","journal-title":"Parasitology"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s00436-010-1761-x","article-title":"Irritable bowel syndrome: is it associated with genotypes of Blastocystis hominis","volume":"106","author":"J Yakoob","year":"2010","journal-title":"Parasitol Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1007\/s00436-011-2626-7","article-title":"Blastocystis infection is associated with irritable bowel syndrome in a Mexican patient population","volume":"110","author":"DE Jimenez-Gonzalez","year":"2012","journal-title":"Parasitol Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.actatropica.2015.05.004","article-title":"Blastocystis and urticaria: Examination of subtypes and morphotypes in an unusual clinical manifestation","volume":"148","author":"RD Casero","year":"2015","journal-title":"Acta Trop"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/MAJ.0b013e3182801478","article-title":"Blastocystis hominis associated acute urticaria","volume":"346","author":"R Verma","year":"2013","journal-title":"Am J Med Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.meegid.2013.07.020","article-title":"Blastocystis subtypes detected in humans and animals from Colombia","volume":"22","author":"JD Ramirez","year":"2014","journal-title":"Infect Genet Evol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1128\/CMR.00022-08","article-title":"New insights on classification, identification, and clinical relevance of Blastocystis spp","volume":"21","author":"KS Tan","year":"2008","journal-title":"Clin Microbiol Rev"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.pt.2007.01.004","article-title":"Terminology for Blastocystis subtypes\u2014a consensus","volume":"23","author":"CR Stensvold","year":"2007","journal-title":"Trends Parasitol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00436-010-2244-9","article-title":"Development of a new PCR protocol to detect and subtype Blastocystis spp. from humans and animals","volume":"109","author":"M Santin","year":"2011","journal-title":"Parasitol Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/cid\/cir810","article-title":"Blastocystis: to treat or not to treat","volume":"54","author":"CM Coyle","year":"2012","journal-title":"Clin Infect Dis"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1128\/JCM.02520-15","article-title":"Blastocystis in Health and Disease: Are We Moving from a Clinical to a Public Health Perspective?","volume":"54","author":"LO Andersen","year":"2016","journal-title":"J Clin Microbiol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1089\/fpd.2012.1177","article-title":"A hospital-based study of epidemiological and clinical data on Blastocystis hominis infection","volume":"9","author":"P Laodim","year":"2012","journal-title":"Foodborne Pathog Dis"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s15010-011-0155-z","article-title":"Epidemiological, clinical, and diagnostic data on intestinal infections with Entamoeba histolytica and Entamoeba dispar among returning travelers","volume":"39","author":"KH Herbinger","year":"2011","journal-title":"Infection"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e84372","DOI":"10.1371\/journal.pone.0084372","article-title":"Subtype distribution of Blastocystis isolates in Sebha, Libya","volume":"8","author":"AM Abdulsalam","year":"2013","journal-title":"PLoS One"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1007\/s00436-012-3218-x","article-title":"Subtype identification of Blastocystis spp. isolated from patients in a major hospital in northeastern Thailand","volume":"112","author":"S Jantermtor","year":"2013","journal-title":"Parasitol Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1177\/2049936113504754","article-title":"Blastocystis, an unrecognized parasite: an overview of pathogenesis and diagnosis","volume":"1","author":"I Wawrzyniak","year":"2013","journal-title":"Ther Adv Infect Dis"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1757-4749-6-17","article-title":"Update on the pathogenic potential and treatment options for Blastocystis sp","volume":"6","author":"T Roberts","year":"2014","journal-title":"Gut Pathog"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4114","DOI":"10.1128\/IAI.00328-06","article-title":"Blastocystis ratti induces contact-independent apoptosis, F-actin rearrangement, and barrier function disruption in IEC-6 cells","volume":"74","author":"MK Puthia","year":"2006","journal-title":"Infect Immun"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1111\/j.1462-5822.2012.01814.x","article-title":"Statin pleiotropy prevents rho kinase-mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases","volume":"14","author":"H Mirza","year":"2012","journal-title":"Cell Microbiol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1128\/EC.00371-07","article-title":"Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kappaB-dependent manner","volume":"7","author":"MK Puthia","year":"2008","journal-title":"Eukaryot Cell"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00436-009-1373-5","article-title":"Expression of interferon gamma and proinflammatory cytokines in the cecal mucosa of rats experimentally infected with Blastocystis sp. strain RN94-9","volume":"105","author":"A Iguchi","year":"2009","journal-title":"Parasitol Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s004360050256","article-title":"Experimental Blastocystis hominis infection in laboratory mice","volume":"83","author":"KT Moe","year":"1997","journal-title":"Parasitol Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1128\/IAI.02279-14","article-title":"Differential regulation of proinflammatory cytokine expression by mitogen-activated protein kinases in macrophages in response to intestinal parasite infection","volume":"82","author":"MX Lim","year":"2014","journal-title":"Infect Immun"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s00436-005-1461-0","article-title":"Degradation of human secretory immunoglobulin A by Blastocystis","volume":"97","author":"MK Puthia","year":"2005","journal-title":"Parasitol Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1074\/jbc.M109.049064","article-title":"Blastocystis legumain is localized on the cell surface, and specific inhibition of its activity implicates a pro-survival role for the enzyme","volume":"285","author":"B Wu","year":"2010","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.parint.2012.02.007","article-title":"Characterization of two cysteine proteases secreted by Blastocystis ST7, a human intestinal parasite","volume":"61","author":"I Wawrzyniak","year":"2012","journal-title":"Parasitol Int"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.tim.2011.10.001","article-title":"Microbial adhesins to gastrointestinal mucus","volume":"20","author":"N Juge","year":"2012","journal-title":"Trends Microbiol"},{"key":"ref33","first-page":"209163","article-title":"Strain-dependent induction of human enterocyte apoptosis by blastocystis disrupts epithelial barrier and ZO-1 organization in a caspase 3- and 9-dependent manner","volume":"2014","author":"Z Wu","year":"2014","journal-title":"Biomed Res Int"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"e2885","DOI":"10.1371\/journal.pntd.0002885","article-title":"Intra-subtype variation in enteroadhesion accounts for differences in epithelial barrier disruption and is associated with metronidazole resistance in Blastocystis subtype-7","volume":"8","author":"Z Wu","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrmicro2538","article-title":"Mucin dynamics and enteric pathogens","volume":"9","author":"MA McGuckin","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1159\/000354683","article-title":"Mucus and the goblet cell","volume":"31","author":"ME Johansson","year":"2013","journal-title":"Dig Dis"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s004360050255","article-title":"Description of a Blastocystis species from Rattus norvegicus","volume":"83","author":"XQ Chen","year":"1997","journal-title":"Parasitol Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.parint.2006.12.004","article-title":"Infectivity of different genotypes of human Blastocystis hominis isolates in chickens and rats","volume":"56","author":"A Iguchi","year":"2007","journal-title":"Parasitol Int"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1007\/s00436-014-3787-y","article-title":"Blastocystis tropism in the pig intestine","volume":"113","author":"R Fayer","year":"2014","journal-title":"Parasitol Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e103962","DOI":"10.1371\/journal.pone.0103962","article-title":"Location and pathogenic potential of Blastocystis in the porcine intestine","volume":"9","author":"W Wang","year":"2014","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nprot.2008.245","article-title":"Use of human tissue explants to study human infectious agents","volume":"4","author":"JC Grivel","year":"2009","journal-title":"Nat Protoc"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/mi.2014.89","article-title":"Subversion of human intestinal mucosa innate immunity by a Crohn's disease-associated E. coli","volume":"8","author":"A Jarry","year":"2015","journal-title":"Mucosal Immunol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e551","DOI":"10.1371\/journal.pntd.0000551","article-title":"An ex-vivo human intestinal model to study Entamoeba histolytica pathogenesis","volume":"3","author":"D Bansal","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1007\/BF00932249","article-title":"Axenic culture of Blastocystis hominis in Iscove's modified Dulbecco's medium","volume":"79","author":"LC Ho","year":"1993","journal-title":"Parasitol Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1472-765X.2009.02729.x","article-title":"Comparison of in vitro models to study bacterial adhesion to the intestinal epithelium","volume":"49","author":"JM Laparra","year":"2009","journal-title":"Lett Appl Microbiol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/onc.2015.74","article-title":"DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis","volume":"35","author":"CW Png","year":"2016","journal-title":"Oncogene"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s004360050517","article-title":"Development of Blastocystis hominis cysts into vacuolar forms in vitro","volume":"85","author":"KT Moe","year":"1999","journal-title":"Parasitol Res"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"e36378","DOI":"10.1371\/journal.pone.0036378","article-title":"Human gastric mucins differently regulate Helicobacter pylori proliferation, gene expression and interactions with host cells","volume":"7","author":"EC Skoog","year":"2012","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1099\/jmm.0.47752-0","article-title":"Campylobacter jejuni response to human mucin MUC2: modulation of colonization and pathogenicity determinants","volume":"57","author":"QV Tu","year":"2008","journal-title":"J Med Microbiol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4161\/gmic.26680","article-title":"Interaction of microbes with mucus and mucins: recent developments","volume":"5","author":"J Naughton","year":"2014","journal-title":"Gut Microbes"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"9298","DOI":"10.1073\/pnas.0600623103","article-title":"Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel","volume":"103","author":"ME Lidell","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"e1856","DOI":"10.1371\/journal.pntd.0001856","article-title":"Serine protease(s) secreted by the nematode Trichuris muris degrade the mucus barrier","volume":"6","author":"SZ Hasnain","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"764","DOI":"10.3390\/pathogens4040764","article-title":"Disruptions of Host Immunity and Inflammation by Giardia Duodenalis: Potential Consequences for Co-Infections in the Gastro-Intestinal Tract","volume":"4","author":"JA Cotton","year":"2015","journal-title":"Pathogens"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"e3952","DOI":"10.1371\/journal.pone.0003952","article-title":"Mucin dynamics in intestinal bacterial infection","volume":"3","author":"SK Linden","year":"2008","journal-title":"PLoS One"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4161\/gmic.28793","article-title":"Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis","volume":"5","author":"G Lennon","year":"2014","journal-title":"Gut Microbes"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1136\/gutjnl-2012-303207","article-title":"Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis","volume":"63","author":"ME Johansson","year":"2014","journal-title":"Gut"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4161\/gmic.1.1.10470","article-title":"The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria","volume":"1","author":"GC Hansson","year":"2010","journal-title":"Gut Microbes"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00436-007-0808-0","article-title":"Predominance of subtype 3 among Blastocystis isolates from a major hospital in Singapore","volume":"102","author":"KH Wong","year":"2008","journal-title":"Parasitol Res"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"25255","DOI":"10.1038\/srep25255","article-title":"Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota","volume":"6","author":"C Audebert","year":"2016","journal-title":"Sci Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0160458","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T14:01:45Z","timestamp":1589032905000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0160458"}},"subtitle":[],"editor":[{"given":"Laurent","family":"Renia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,8,10]]},"references-count":59,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0160458","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,10]]}}}