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The standard therapeutic interventions for colitis have focused mainly on maintaining the remission levels of the disease. Nonetheless, such treatment strategies (using anti\u2010inflammatory, immunomodulatory agents) do not address colitis' root cause, especially the mucosal damage and dysregulated intestinal barrier functions. Restoration of barrier functionality by mucosal healing or physical barrier protecting strategies shall be considered as an initial event in the disease suppression and progression. Herein, a biphasic hyaluronan (HA) enema suspension, na\u00efve\u2010HA systems that protect the dysregulated gut epithelium by decreasing the inflammation, permeability, and helping in maintaining the epithelial barrier integrity in the dextran sodium sulfate\u2010induced colitis mice model is reported. Furthermore, HA\u2010based system modulates intestinal epithelial junctional proteins and regulatory signaling pathways, resulting in attenuation of inflammation and mucosal protection. The results suggest that HA\u2010based system can be delivered as an enema to act as a barrier protecting system for managing distal colonic inflammatory diseases, including colitis.<\/jats:p>","DOI":"10.1002\/advs.202103189","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:29:24Z","timestamp":1636590564000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Modulation of Gut Barrier Functions in Ulcerative Colitis by Hyaluronic Acid System"],"prefix":"10.1002","volume":"9","author":[{"given":"Niranjan G.","family":"Kotla","sequence":"first","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices National University of Ireland Galway  Galway H91 W2TY Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isma Liza Mohd","family":"Isa","sequence":"additional","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices National University of Ireland Galway  Galway H91 W2TY Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha","family":"Rasala","sequence":"additional","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices National University of Ireland Galway  Galway H91 W2TY Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Secil","family":"Demir","sequence":"additional","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices National University of Ireland Galway  Galway H91 W2TY Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajbir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology James Graham Brown Cancer Center University of Louisville  Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becca V.","family":"Baby","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology James Graham Brown Cancer Center University of Louisville  Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha K.","family":"Swamy","sequence":"additional","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices National University of Ireland Galway  Galway H91 W2TY Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dockery","sequence":"additional","affiliation":[{"name":"Department of Anatomy National University of Ireland  Galway H91 TK33 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatakrishna R.","family":"Jala","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology James Graham Brown Cancer Center University of Louisville  Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury","family":"Rochev","sequence":"additional","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices National University of Ireland Galway  Galway H91 W2TY Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-4933","authenticated-orcid":false,"given":"Abhay","family":"Pandit","sequence":"additional","affiliation":[{"name":"C\u00daRAM, SFI Research Centre for Medical Devices National University of Ireland Galway  Galway H91 W2TY Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-018-0063-z"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0992-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2018.09.013"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01094"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-017-0122-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13771"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.04062.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1070-x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2015.13.1.11"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0461-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198902093200606"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-0898com"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.7.4641"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113938"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21048"},{"key":"e_1_2_9_16_1","first-page":"2597","volume":"14","author":"Catalan\u2010Serra I.","year":"2018","journal-title":"Hum. 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