{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:20Z","timestamp":1792787600343,"version":"4.5.0"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"name":"NIH","award":["DE021578,DE023967,NIH Intramural program"],"award-info":[{"award-number":["DE021578,DE023967,NIH Intramural program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,6]]},"abstract":"<jats:p>\n                    Studies in patients with genetic defects can provide unique insights regarding the role of specific genes and pathways in humans. Patients with defects in the Th17\/IL-17 axis, such as patients harboring loss-of-function\n                    <jats:italic>STAT3<\/jats:italic>\n                    mutations (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral fungal infections. Our studies aimed to comprehensively evaluate consequences of\n                    <jats:italic>STAT3<\/jats:italic>\n                    deficiency on the oral commensal microbiome. We characterized fungal and bacterial communities in AD-HIES in the presence and absence of oral fungal infection compared with healthy volunteers. Analyses of oral mucosal fungal communities in AD-HIES revealed severe dysbiosis with dominance of\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    (\n                    <jats:italic>C. albicans<\/jats:italic>\n                    ) in actively infected patients and minimal representation of health-associated fungi and\/or opportunists. Bacterial communities also displayed dysbiosis in AD-HIES, particularly in the setting of active\n                    <jats:italic>Candida<\/jats:italic>\n                    infection. Active candidiasis was associated with decreased microbial diversity and enrichment of the streptococci\n                    <jats:italic>Streptococcus oralis<\/jats:italic>\n                    (\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>oralis<\/jats:italic>\n                    ) and\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>mutans,<\/jats:italic>\n                    suggesting an interkingdom interaction of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    with oral streptococci. Increased abundance of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>mutans<\/jats:italic>\n                    was consistent with susceptibility to dental caries in AD-HIES. Collectively, our findings illustrate a critical role for STAT3\/Th17 in the containment of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    as a commensal organism and an overall contribution in the establishment of fungal and bacterial oral commensal communities.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.122061","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T11:02:36Z","timestamp":1536145356000},"source":"Crossref","is-referenced-by-count":67,"title":["Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis"],"prefix":"10.1172","volume":"3","author":[{"given":"Loreto","family":"Abusleme","sequence":"first","affiliation":[{"name":"Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, Maryland, USA."},{"name":"Faculty of Dentistry, University of Chile, Santiago, Chile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia I.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Department of Oral Health and Diagnostic Sciences, UConn Health Center, Farmington, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra F.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology (LCIM),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Greenwell-Wild","sequence":"additional","affiliation":[{"name":"Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Brenchley","sequence":"additional","affiliation":[{"name":"Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jigar V.","family":"Desai","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section, NIAID,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weng-Ian","family":"Ng","sequence":"additional","affiliation":[{"name":"Microbial Genomics Section, NHGRI, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Holland","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology (LCIM),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail S.","family":"Lionakis","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section, NIAID,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A.","family":"Segre","sequence":"additional","affiliation":[{"name":"Microbial Genomics Section, NHGRI, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi H.","family":"Kong","sequence":"additional","affiliation":[{"name":"Cutaneous Microbiome and Inflammation Section, NIAMS, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki M.","family":"Moutsopoulos","sequence":"additional","affiliation":[{"name":"Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515583533"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.11.051"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.008"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3182"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260144"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nri3608"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature11234"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12598"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.08.005"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903739"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200439"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.09.002"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141065"},{"issue":"6","key":"B15","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a019638","article-title":"Mendelian genetics of human susceptibility to fungal infection","volume":"4","author":"Lionakis","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.09.003"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.019"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061308"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130318"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081463"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.57"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073687"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature06096"},{"issue":"7445","key":"B24","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S0140-6736(66)90119-X","article-title":"Job\u2019s Syndrome. Recurrent, \u201ccold\u201d, staphylococcal abscesses","volume":"1","author":"Davis","year":"1966","journal-title":"Lancet"},{"issue":"1","key":"B25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1542\/peds.49.1.59","article-title":"Extreme hyperimmunoglobulinemia E and undue susceptibility to infection","volume":"49","author":"Buckley","year":"1972","journal-title":"Pediatrics"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903043400904"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0b013e31825f95b9"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C600321200"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.05.003"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nature06764"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080218"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.5"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.007"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.10.001"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1101\/gr.159467.113"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1159\/000351912"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60917-9"},{"issue":"4","key":"B38","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1080\/714031126","article-title":"Distinct protective host defenses against oral and vaginal candidiasis","volume":"40","author":"Fidel","year":"2002","journal-title":"Med Mycol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/BF00157408"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1252015"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000713"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090899"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003996"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nature12171"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042770"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0487-y"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05896-11"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00087-14"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12216"},{"issue":"10","key":"B50","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003616","article-title":"Streptococcus mutans, Candida albicans, and the human mouth: a sticky situation","volume":"9","author":"Metwalli","year":"2013","journal-title":"PLoS Pathog"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1159\/000324809"},{"key":"B52","article-title":"Candida albicans stimulates Streptococcus mutans microcolony development via cross-kingdom biofilm-derived metabolites","volume":"7","author":"Kim","year":"2017","journal-title":"Sci Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2012.05.012"},{"issue":"3","key":"B54","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000314675","article-title":"Association of oral candidal carriage with dental caries in children","volume":"44","author":"Raja","year":"2010","journal-title":"Caries Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-015-0134-3"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2006.06.001"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12453"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2012.04.005"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.3366"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.7.4102-4108.2004"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1086\/302547"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.05.130"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/2049-2618-2-6"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01541-09"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01043-13"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr381"},{"key":"B67","doi-asserted-by":"crossref","DOI":"10.1093\/database\/baq013","article-title":"The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information","volume":"2010","author":"Chen","year":"2010","journal-title":"Database (Oxford)"},{"key":"B68","doi-asserted-by":"crossref","DOI":"10.3402\/jom.v7.28934","article-title":"Robust species taxonomy assignment algorithm for 16S rRNA NGS reads: application to oral carcinoma samples","volume":"7","author":"Al-Hebshi","year":"2015","journal-title":"J Oral Microbiol"},{"key":"B69","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-11-538","article-title":"pplacer: linear time maximum-likelihood and Bayesian phylogenetic placement of sequences onto a fixed reference tree","volume":"11","author":"Matsen","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2012.174"},{"key":"B71","doi-asserted-by":"crossref","DOI":"10.1186\/2049-2618-2-40","article-title":"Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis","volume":"2","author":"Willger","year":"2014","journal-title":"Microbiome"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.014"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-6-r60"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/122061\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:41:54Z","timestamp":1779194514000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/122061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,6]]},"references-count":73,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2018,9,6]]},"published-print":{"date-parts":[[2018,9,6]]}},"alternative-id":["10.1172\/jci.insight.122061"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.122061","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,6]]},"article-number":"e122061"}}