{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:28:34Z","timestamp":1790278114090,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"publisher","award":["S3301743"],"award-info":[{"award-number":["S3301743"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2017R1A5A2014768"],"award-info":[{"award-number":["2017R1A5A2014768"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea Healthy Industry Development Institute","award":["22203MFDS539"],"award-info":[{"award-number":["22203MFDS539"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (<jats:italic>Lactobacillus plantarum<\/jats:italic> NK151 and <jats:italic>Bifidobacterium bifidum<\/jats:italic> NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision\/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-\u03b1, IL-1\u03b2, and MMP-9 expression, TNF-\u03b1<jats:sup>+<\/jats:sup> and NF-\u03baB<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup> cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-\u03b1 and IL-1\u03b2 expression and NF-\u03baB<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup> cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-\u03b1, IL-1\u03b2, and MMP-9 expression and TNF-\u03b1<jats:sup>+<\/jats:sup> and NF-\u03baB<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup> cell populations in the conjunctiva and TNF-\u03b1 and IL-1\u03b2 expression and NF-\u03baB<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup> cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-\u03b1, IL-1\u03b2, and MMP-9 expression, TNF-\u03b1<jats:sup>+<\/jats:sup> and NF-\u03baB<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup> cell populations, and edema in the conjunctiva and TNF-\u03b1 and IL-1\u03b2 expression and NF-\u03baB<jats:sup>+<\/jats:sup>CD11c<jats:sup>+<\/jats:sup> cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed <jats:italic>Muribaculaceae<\/jats:italic>, <jats:italic>Prevotellaceae<\/jats:italic>, and <jats:italic>Lactobacillaceae<\/jats:italic> populations in the gut microbiota, while eFMT-induced <jats:italic>Bacteroidaceae<\/jats:italic> population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-\u03b1 and IL-1\u03b2 with the regulation of gut microbiota-involved NF-\u03baB signaling.<\/jats:p>","DOI":"10.1371\/journal.pone.0303423","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T17:55:13Z","timestamp":1718646913000},"page":"e0303423","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Probiotic LB101 alleviates dry eye in mice by suppressing matrix metalloproteinase-9 expression through the regulation of gut microbiota-involved NF-\u03baB 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Moon","year":"2020","journal-title":"Int J Mol Sci."},{"issue":"1","key":"pone.0303423.ref012","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1080\/07853890.2021.1925150","article-title":"Influence of gut microbiota on eye diseases: an overview","volume":"53","author":"P Napolitano","year":"2021","journal-title":"Ann Med"},{"issue":"9","key":"pone.0303423.ref013","doi-asserted-by":"crossref","first-page":"e0001421","DOI":"10.1128\/IAI.00014-21","article-title":"Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis","volume":"89","author":"J Zou","year":"2021","journal-title":"Infect Immun"},{"issue":"6","key":"pone.0303423.ref014","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/mp.2016.50","article-title":"From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways","volume":"21","author":"GB Rogers","year":"2016","journal-title":"Mol 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Ter"},{"issue":"7","key":"pone.0303423.ref021","doi-asserted-by":"crossref","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"18","author":"N Percie du Sert","year":"2020","journal-title":"PLoS Biol"},{"issue":"10","key":"pone.0303423.ref022","article-title":"The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175.","volume":"14","author":"JW Yoo","year":"2022","journal-title":"Nutrients."},{"key":"pone.0303423.ref023","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fimmu.2020.00273","article-title":"Interplay Between Human Gut Bacteria Escherichia coli and Lactobacillus mucosae in the Occurrence of Neuropsychiatric Disorders in Mice.","volume":"11","author":"JK Kim","year":"2020","journal-title":"Front ImmunolEpub"},{"issue":"5","key":"pone.0303423.ref024","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/s41385-018-0042-3","article-title":"Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice.","volume":"11","author":"HM Jang","year":"2018","journal-title":"Mucosal Immunol."},{"issue":"5","key":"pone.0303423.ref025","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1142\/S0192415X17500550","article-title":"The Mixture of Anemarrhena asphodeloides and Coptis chinensis Attenuates High-Fat Diet-Induced Colitis in Mice","volume":"45","author":"SM Lim","year":"2017","journal-title":"Am J Chin Med"},{"issue":"Pt 1","key":"pone.0303423.ref026","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1099\/00221287-148-1-257","article-title":"Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set.","volume":"148","author":"MA Nadkarni","year":"2002","journal-title":"Microbiology (Reading)."},{"issue":"7","key":"pone.0303423.ref027","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1128\/JCM.42.7.3128-3136.2004","article-title":"Quantitative analysis of diverse Lactobacillus species present in advanced dental caries","volume":"42","author":"R Byun","year":"2004","journal-title":"J Clin Microbiol"},{"issue":"1","key":"pone.0303423.ref028","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41467-022-35767-4","article-title":"Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection","volume":"14","author":"R Le Guern","year":"2023","journal-title":"Nat Commun"},{"issue":"10","key":"pone.0303423.ref029","doi-asserted-by":"crossref","first-page":"113220","DOI":"10.1016\/j.celrep.2023.113220","article-title":"Supplementation with a high-glucose drink stimulates anti-tumor immune responses to glioblastoma via gut microbiota modulation","volume":"42","author":"J Kim","year":"2023","journal-title":"Cell Rep"},{"issue":"11","key":"pone.0303423.ref030","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1128\/JCM.42.11.5238-5244.2004","article-title":"Carious dentine provides a habitat for a complex array of novel Prevotella-like bacteria","volume":"42","author":"MA Nadkarni","year":"2004","journal-title":"J Clin Microbiol"},{"issue":"3","key":"pone.0303423.ref031","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0014-4835(03)00204-5","article-title":"Distribution of mucins at the ocular surface","volume":"78","author":"IK Gipson","year":"2004","journal-title":"Exp Eye Res"},{"key":"pone.0303423.ref032","first-page":"29","article-title":"Innate defense of the ocular surface.","volume":"9","author":"NA McNamara","year":"2003","journal-title":"Eye Contact Lens"},{"issue":"1","key":"pone.0303423.ref033","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1097\/ICO.0b013e31817f2a7f","article-title":"Innate immunity of the ocular surface and ocular surface inflammatory disorders","volume":"27","author":"M. Ueta","year":"2008","journal-title":"Cornea"},{"issue":"5","key":"pone.0303423.ref034","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1167\/tvst.7.5.31","article-title":"Matrix Metalloproteinase 9 Point-of-Care Immunoassay Result Predicts Response to Topical Cyclosporine Treatment in Dry Eye Disease.","volume":"7","author":"JY Park","year":"2018","journal-title":"Transl Vis Sci Technol."},{"issue":"2","key":"pone.0303423.ref035","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jtos.2015.10.004","article-title":"The Matrix Metalloproteinase 9 Point-of-Care Test in Dry Eye.","volume":"14","author":"NL Lanza","year":"2016","journal-title":"Ocul Surf."},{"issue":"3","key":"pone.0303423.ref036","doi-asserted-by":"crossref","first-page":"e57955","DOI":"10.1371\/journal.pone.0057955","article-title":"IL-1\u03b2 promotes corneal epithelial cell migration by increasing MMP-9 expression through NF-\u03baB- and AP-1-dependent pathways.","volume":"8","author":"HC Tseng","year":"2013","journal-title":"PLoS One."},{"issue":"4","key":"pone.0303423.ref037","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1006\/exer.2001.1054","article-title":"Regulation of MMP-9 production by human corneal epithelial cells","volume":"73","author":"DQ Li","year":"2001","journal-title":"Exp Eye Res"},{"issue":"2","key":"pone.0303423.ref038","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1136\/bjo.85.2.147","article-title":"Tear film MMP accumulation and corneal disease","volume":"85","author":"VA Smith","year":"2001","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"pone.0303423.ref039","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1167\/iovs.61.3.42","article-title":"IRT5 Probiotics Changes Immune Modulatory Protein Expression in the Extraorbital Lacrimal Glands of an Autoimmune Dry Eye Mouse Model","volume":"61","author":"SH Choi","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0303423.ref040","doi-asserted-by":"crossref","first-page":"852918","DOI":"10.3389\/fmed.2022.852918","article-title":"Gut Microbiota From Sj\u00f6gren syndrome Patients Causes Decreased T Regulatory Cells in the Lymphoid Organs and Desiccation-Induced Corneal Barrier Disruption in Mice.","volume":"9","author":"L Schaefer","year":"2022","journal-title":"Front Med (Lausanne)."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0303423","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T17:55:55Z","timestamp":1718646955000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0303423"}},"subtitle":[],"editor":[{"given":"Joseph L.","family":"Roberts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,6,17]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0303423","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,17]]}}}