{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:30:23Z","timestamp":1793035823051,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T00:00:00Z","timestamp":1598313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-\u03b1 and\/or IFN-\u03b3 was significantly increased in mice that had been administered antibiotics. TNF-\u03b1 and IFN-\u03b3 stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-\u03b1 and\/or IFN-\u03b3 expression in mice.<\/jats:p>","DOI":"10.3390\/ijms21176108","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T09:24:56Z","timestamp":1598347496000},"page":"6108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis"],"prefix":"10.3390","volume":"21","author":[{"given":"Ying","family":"Ran","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"},{"name":"Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"},{"name":"Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"},{"name":"Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Ebisutani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Biofermin Pharmaceutical Co., Ltd., 7-3-4, Higashi-machi, Ibukidai, Nishi-ku, Kobe 651-2242, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Maeda","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Biofermin Pharmaceutical Co., Ltd., 7-3-4, Higashi-machi, Ibukidai, Nishi-ku, Kobe 651-2242, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Makizaki","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Biofermin Pharmaceutical Co., Ltd., 7-3-4, Higashi-machi, Ibukidai, Nishi-ku, Kobe 651-2242, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ohno","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Biofermin Pharmaceutical Co., Ltd., 7-3-4, Higashi-machi, Ibukidai, Nishi-ku, Kobe 651-2242, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Kono","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Tozawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-932X","authenticated-orcid":false,"given":"Tadayuki","family":"Oshima","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Miwa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3389\/fimmu.2017.00598","article-title":"Leaky gut as a danger signal for autoimmune diseases","volume":"8","author":"Mu","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1007\/s00535-016-1207-z","article-title":"Gastrointestinal mucosal barrier function and diseases","volume":"51","author":"Oshima","year":"2016","journal-title":"J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nri3738","article-title":"Regional specialization within the intestinal immune system","volume":"14","author":"Mowat","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.it.2011.04.003","article-title":"The intestinal epithelial barrier in the control of homeostasis and immunity","volume":"32","author":"Rescigno","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1128\/IAI.01104-10","article-title":"Antibiotic treatment alters the colonic mucus layer and predisposes the host to exacerbated Citrobacter rodentium-induced colitis","volume":"79","author":"Wlodarska","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1136\/gutjnl-2019-318427","article-title":"Leaky gut: Mechanisms, measurement and clinical implications in humans","volume":"68","author":"Camilleri","year":"2019","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Obrenovich, M.E.M. (2018). Leaky gut, leaky brain?. Microorganism, 6.","DOI":"10.3390\/microorganisms6040107"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.12938\/bmfh.19-023","article-title":"Interaction of the microbiota with the human body in health and diseases","volume":"39","author":"Yildiz","year":"2020","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature11551","article-title":"Reciprocal interactions of the intestinal microbiota and immune system","volume":"489","author":"Maynard","year":"2012","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12929-018-0483-8","article-title":"Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: Exploring a common ground hypothesis","volume":"25","author":"Yu","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1038\/s41598-019-40978-9","article-title":"Alteration of GLP-1\/GPR43 expression and gastrointestinal motility in dysbiotic mice treated with vancomycin","volume":"9","author":"Xu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12384","DOI":"10.1038\/s41598-018-30943-3","article-title":"Effect of probiotic Bifidobacterium bifidum G9-1 on the relationship between gut microbiota profile and stress sensitivity in maternally separated rats","volume":"8","author":"Fukui","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_13","first-page":"2591","article-title":"Colonic M1 macrophage is associated with the prolongation of gastrointestinal motility and obesity in mice treated with vancomycin","volume":"19","author":"Inoue","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Niccolai, E., Boem, F., Russo, E., and Amedei, A. (2019). The gut-brain Axis in the neuropsychological disease model of obesity: A classical movie revised by the emerging director \u201cmicrobiome\u201d. Nutrients, 11.","DOI":"10.3390\/nu11010156"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jevs.2017.02.009","article-title":"Alterations in intestinal permeability: The role of the \u201cLeaky Gut\u201d in health and disease","volume":"52","author":"Stewart","year":"2017","journal-title":"J. Equine Vet. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tulstrup, M.V., Christensen, E.G., Carvalho, V., Linninge, C., Ahrn\u00e9, S., H\u00f8jberg, O., Licht, T.R., and Bahl, M.I. (2015). Antibiotic treatment affects intestinal permeability and gut microbial composition in Wistar rats dependent on antibiotic class. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144854"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.jhep.2013.11.034","article-title":"Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity","volume":"60","author":"Vrieze","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_18","first-page":"686","article-title":"The intestinal barrier function and its involvement in digestive disease","volume":"107","author":"Vicario","year":"2015","journal-title":"Rev. Esp. Enferm. Dig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.pharmthera.2016.04.007","article-title":"Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis","volume":"164","author":"Sivaprakasam","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1007\/s10620-012-2259-4","article-title":"Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription","volume":"57","author":"Wang","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Martin-Gallausiaux, C., Marinelli, L., Blotti\u00e8re, H.M., Larraufie, P., and Lapaque, N. (2020). SCFA: Mechanisms and functional importance in the gut. Proc. Nutr. Soc., 1\u201313. Online ahead of print.","DOI":"10.1017\/S0029665120006916"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4726","DOI":"10.1128\/IAI.00319-08","article-title":"Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection","volume":"76","author":"Sekirov","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"G736","DOI":"10.1152\/ajpgi.00362.2014","article-title":"Expression of Reg family genes in the gastrointestinal tract of mice treated with indomethacin","volume":"308","author":"Sun","year":"2015","journal-title":"Am. J. Physiol.-Gastrointest Liver Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.trsl.2016.03.007","article-title":"Role of regenerating gene I in claudin expression and barrier function in the small intestine","volume":"173","author":"Kitayama","year":"2016","journal-title":"Transl. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G367","DOI":"10.1152\/ajpgi.00232.2016","article-title":"Involvement of gut microbiota in association between GLP-1\/GLP-1 receptor expression and gastrointestinal motility","volume":"312","author":"Yang","year":"2017","journal-title":"Am. J. Physiol.-Gastrointest Liver Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1046\/j.1350-1925.2003.00451.x","article-title":"Influence of sex and experimental protocol on the effect of maternal deprivation on rectal sensitivity to distension in the adult rat","volume":"15","author":"Rosztoczy","year":"2003","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/AEM.70.1.167-173.2004","article-title":"Quantitative PCR with 16S rRNA-gene-targeted species-specific primers for analysis of human intestinal bifidobacteria","volume":"70","author":"Matsuki","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kawahara, T., Makizaki, Y., Oikawa, Y., Tanaka, Y., Maeda, A., Shimakawa, M., Komoto, S., Moriguchi, K., Ohno, H., and Taniguchi, K. (2017). Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173979"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"335","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"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/17\/6108\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:06:13Z","timestamp":1760177173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/17\/6108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,25]]},"references-count":29,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21176108"],"URL":"https:\/\/doi.org\/10.3390\/ijms21176108","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,25]]}}}