{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:11:05Z","timestamp":1787166665096,"version":"build-2736575974"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A2B2007209"],"award-info":[{"award-number":["2017R1A2B2007209"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the clinical effects of IRT5 probiotics in the environmental dry eye model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eight week old male C57BL\/6 mice were randomly divided into two groups; control group (n = 16) received oral gavage of 300 \u03bcL phosphate-buffered saline (PBS) alone once daily, IRT5 group (n = 9) received oral gavage of 1 x 10\n                      <jats:sup>9<\/jats:sup>\n                      CFU IRT5 probiotics powder in 300 \u03bcL PBS once daily, both groups for 11 to 12 days. Simultaneously, all mice underwent dry eye induction. Tear secretion, corneal staining and conjunctival goblet cell density were evaluated. Quantative real-time polymerase chain reaction (RT-PCR) for inflammation-related markers was performed. 16S ribosomal RNA of fecal microbiome was analyzed and compositional difference, alpha and beta diversities were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was no difference in NEI score but significant increase in tear secretion was observed in IRT5 group (p &lt; 0.001). There was no significant difference in goblet cell density between groups. Quantative RT-PCR of cornea and conjunctiva revealed increased TNF-\u03b1 expression in IRT5 group (p &lt; 0.001) whereas other markers did not significantly differ from control. IRT5 group had significantly increased species diversity by Shannon index (p = 0.041). Beta diversity of genus by UniFrac principle coordinates analysis showed significant distance between groups (p = 0.001). Compositional differences between groups were observed and some were significantly associated with tear secretion. Multivariate linear regression analysis revealed\n                      <jats:italic>Christensenellaceae<\/jats:italic>\n                      (p = 0.009),\n                      <jats:italic>Lactobacillus Helveticus group<\/jats:italic>\n                      (p = 0.002) and\n                      <jats:italic>PAC001797_s<\/jats:italic>\n                      (p = 0.011) to strongly influence tear secretion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In experimental dry eye model, IRT5 probiotics treatment partially improves experimental dry eye by increasing tear secretion which was associated with and influenced by the change in intestinal microbiome. Also, intestinal microbiome may affect the lacrimal gland through a different mechanism other than regulating inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0243176","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T15:34:19Z","timestamp":1606836859000},"page":"e0243176","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Effect of IRT5 probiotics on dry eye in the experimental dry eye mouse model"],"prefix":"10.1371","volume":"15","author":[{"given":"Jayoon","family":"Moon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Suk","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Yeop","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin-Hyeog","family":"Im","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-6894","authenticated-orcid":true,"given":"Mee Kum","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"issue":"3","key":"pone.0243176.ref001","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"AJ Bron","year":"2017","journal-title":"Ocul Surf"},{"issue":"1","key":"pone.0243176.ref002","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/mi.2013.20","article-title":"Chronic dry eye disease is principally mediated by effector memory Th17 cells","volume":"7","author":"Y Chen","year":"2014","journal-title":"Mucosal Immunol"},{"issue":"1","key":"pone.0243176.ref003","doi-asserted-by":"crossref","first-page":"e000078","DOI":"10.1136\/bmjophth-2017-000078","article-title":"Kinetics of Corneal Antigen Presenting Cells in Experimental Dry Eye Disease","volume":"1","author":"HS Lee","year":"2017","journal-title":"BMJ Open Ophthalmol"},{"key":"pone.0243176.ref004","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.exer.2013.08.013","article-title":"T helper cytokines in dry eye disease","volume":"117","author":"SC Pflugfelder","year":"2013","journal-title":"Exp Eye Res"},{"issue":"4","key":"pone.0243176.ref005","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1167\/iovs.11-9299","article-title":"Autoantibodies contribute to the immunopathogenesis of experimental dry eye disease","volume":"53","author":"ME Stern","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"pone.0243176.ref006","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1167\/iovs.09-3838","article-title":"Desiccating stress promotion of Th17 differentiation by ocular surface tissues through a dendritic cell-mediated pathway","volume":"51","author":"X Zheng","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"pone.0243176.ref007","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.4049\/jimmunol.1101442","article-title":"Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis","volume":"187","author":"CS Schaumburg","year":"2011","journal-title":"J Immunol"},{"issue":"24","key":"pone.0243176.ref008","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1056\/NEJMra1600266","article-title":"The Human Intestinal Microbiome in Health and Disease","volume":"375","author":"SV Lynch","year":"2016","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0243176.ref009","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJMra1003071","article-title":"Microbial genomics and infectious diseases","volume":"365","author":"DA Relman","year":"2011","journal-title":"N Engl J Med"},{"issue":"6252","key":"pone.0243176.ref010","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1126\/science.aad0781","article-title":"MICROBIOME. 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