{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T14:55:23Z","timestamp":1786719323557,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The interplay between host immunity and the microbiome is increasingly recognized as an important factor in ocular surface diseases. Although cutaneous and intestinal dysbiosis have been implicated in atopic dermatitis (AD), the role of the ocular microbiome in its severe ophthalmic manifestation, atopic keratoconjunctivitis (AKC), remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed 16S rRNA gene sequencing to characterize the ocular and fecal microbiota of patients with AD and severe AKC, AD without severe ocular involvement, Stevens\u2013Johnson syndrome (SJS) with severe ocular complications (SOC), and healthy controls. Microbial community composition was compared using principal coordinate analysis (PCoA) and taxonomic profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ocular microbiota composition differed among the study groups. PCoA demonstrated that SJS samples clustered separately from healthy controls, whereas AKC samples occupied an intermediate position between the healthy control and SJS groups. Taxonomic analysis revealed enrichment of Corynebacterium 1 (a SILVA genus-level taxonomic assignment) in SJS, while AKC samples exhibited increased relative abundances of both Corynebacterium 1 and Staphylococcus. In contrast, AD patients without severe ocular involvement maintained an ocular microbial community broadly similar to that of healthy controls, including the presence of Neisseria. Analysis of paired fecal samples did not reveal disease-associated clustering or major compositional differences among the study groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that, using genus-level 16S rRNA sequencing, disease-associated microbial alterations are more readily detected on the ocular surface than in the fecal microbiome in this cohort. The results support a potential contribution of the local ocular microenvironment to microbial signatures associated with immune-mediated ocular surface inflammation and provide a framework for future studies investigating the role of the ocular microbiome in disease pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1887091","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:49:00Z","timestamp":1786715340000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative analysis of microbiota in the ocular surface of patients with atopic keratoconjunctivitis and Stevens-Johnson Syndrome with severe ocular complications"],"prefix":"10.3389","volume":"17","author":[{"given":"Mayumi","family":"Ueta","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Kyoto Prefectural University of Medicine","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Man","family":"Tse","sequence":"additional","affiliation":[{"name":"ROHTO Pharmaceutical Co., Ltd.","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinako","family":"Nanri","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Nishigaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyoto Prefectural University of Medicine","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Takai","sequence":"additional","affiliation":[{"name":"ROHTO Pharmaceutical Co., Ltd.","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki Jujo","family":"Sanada","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Hosomi","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition","place":["Osaka, Japan"]},{"name":"Graduate School of Veterinary Science, Osaka Metropolitan University","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Miyano","sequence":"additional","affiliation":[{"name":"ROHTO Pharmaceutical Co., Ltd.","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Ishii","sequence":"additional","affiliation":[{"name":"ROHTO Pharmaceutical Co., Ltd.","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Sotozono","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyoto Prefectural University of Medicine","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kunisawa","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-022-00551-6","article-title":"Mucosal immunology of the ocular surface","volume":"15","author":"Paiva","year":"2022","journal-title":"Mucosal Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31817f2a7f","article-title":"Innate immunity of the ocular surface and ocular surface inflammatory disorders","volume":"27","author":"Ueta","year":"2008","journal-title":"Cornea"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8071033","article-title":"Current evidence on the ocular surface microbiota and related diseases","volume":"8","author":"Petrillo","year":"2020","journal-title":"Microorganisms"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.759333","article-title":"Microbiota and ocular diseases","volume":"11","author":"Xue","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.536","article-title":"Difference in the plasma level of miR-628-3p in atopic dermatitis patients with\/without atopic keratoconjunctivitis","volume":"9","author":"Ueta","year":"2021","journal-title":"Immun Inflammation Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2008.12.048","article-title":"Diagnosis and treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis with ocular complications","volume":"116","author":"Sotozono","year":"2009","journal-title":"Ophthalmology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.10.029","article-title":"New grading system for the evaluation of chronic ocular manifestations in patients with Stevens-Johnson syndrome","volume":"114","author":"Sotozono","year":"2007","journal-title":"Ophthalmology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ajo.2015.05.002","article-title":"Predictive factors associated with acute ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis","volume":"160","author":"Sotozono","year":"2015","journal-title":"Am J Ophthalmol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.05.003","article-title":"Ocular surface inflammation is regulated by innate immunity","volume":"31","author":"Ueta","year":"2012","journal-title":"Prog Retin Eye Res"},{"key":"B10","article-title":"Critical insights into the ocular surface microbiome: the need to standardize","volume":"47","author":"Clougher","year":"2024","journal-title":"New Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.741654","article-title":"Categorization of the ocular microbiome in Japanese Stevens-Johnson syndrome patients with severe ocular complications","volume":"11","author":"Ueta","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2020.02.006","article-title":"Japanese guidelines for atopic dermatitis","volume":"69","author":"Katoh","year":"2020","journal-title":"Allergol Int"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2020.03.005","article-title":"Japanese guidelines for allergic conjunctival diseases 2020","volume":"69","author":"Miyazaki","year":"2020","journal-title":"Allergol Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/aos.12397","article-title":"Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity","volume":"92","author":"Sotozono","year":"2014","journal-title":"Acta Ophthalmol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/2049-2618-2-6","article-title":"An improved dual-indexing appraoch for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform","volume":"2","author":"Fadrosh","year":"2014","journal-title":"Microbiome"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat Methods"},{"key":"B17","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1186\/s12859-019-3187-5","article-title":"Impact of quality trimming on the efficiency of reads joining and diversity analysis of Illumina paired-end reads in the context of QIIME1 and QIIME2 microbiome analysis frameworks","volume":"20","author":"Mohsen","year":"2019","journal-title":"BMC Bioinf"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00357-014-9161-z","article-title":"Ward's hierarchical agglomerative clustering method: which algorithms implement Ward's criterion","volume":"31","author":"Murtagh","year":"2014","journal-title":"J Classif"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw311","article-title":"PERMANOVA-S: association test for microbial community composition that accommodates confounders and mutliple distances","volume":"32","author":"Tang","year":"2016","journal-title":"Bioinformatics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4353","DOI":"10.1038\/s41598-020-60794-w","article-title":"Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects","volume":"10","author":"Kittipibul","year":"2020","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01552-24","article-title":"An underestimated pathogen: Corynebacterium species","volume":"63","author":"Mitchell","year":"2025","journal-title":"J Clin Microbiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.xjidi.2022.100131","article-title":"Type 2 inflammation contributes to skin barrier dysfunction in atopic dermatitis","volume":"2","author":"Beck","year":"2022","journal-title":"JID Innov"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1480257","article-title":"Understanding the role of Staphylococcus aureus in atopic dermatitis: strain diversity, microevolution, and prophage influences","volume":"11","author":"Wang","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713338","article-title":"Targeting the gut\u2013eye axis: an emerging strategy to face ocular diseases","volume":"24","author":"Campagnoli","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20251046","article-title":"TLR2 supports \u03b3\u03b4 T cell IL-17A response to ocular surface commensals by metabolic reprogramming","volume":"222","author":"Zhu","year":"2025","journal-title":"J Exp Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.immuni.2017.06.014","article-title":"An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal \u03b3\u03b4 T cells","volume":"47","author":"Leger","year":"2017","journal-title":"Immunity"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1887091\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:49:01Z","timestamp":1786715341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1887091\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":27,"alternative-id":["10.3389\/fimmu.2026.1887091"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1887091","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]},"article-number":"1887091"}}