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Current first\u2010line treatments for IBD have limited efficacy and significant side effects. An innovative H<jats:sub>2<\/jats:sub>S\u2010releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide\u2010loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H<jats:sub>2<\/jats:sub>S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2\/HO\u20101, PI3K\u2010AKT, and RAS\/MAPK\/AP\u20101, and inhibiting the p38\/ERK MAPK, p65 NF\u2010\u03baB, and JAK\u2010STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management.<\/jats:p>","DOI":"10.1002\/advs.202308092","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T23:00:39Z","timestamp":1706914839000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["H<sub>2<\/sub>S\u2010Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation"],"prefix":"10.1002","volume":"11","author":[{"given":"Ting","family":"Jin","sequence":"first","affiliation":[{"name":"School and Hospital of Stomatology Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Lu","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ruian People's Hospital The Third Affiliated Hospital of Wenzhou Medical University  Wenzhou 325016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfan","family":"Chen","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyun","family":"Zeng","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Shi","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Research and Engineering Center of Biomedical Materials Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinkun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ruian People's Hospital The Third Affiliated Hospital of Wenzhou Medical University  Wenzhou 325016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3399-3067","authenticated-orcid":false,"given":"Xiaojun","family":"Cai","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32448-0"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjac110"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.150"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx009"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjab178"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04612.x"},{"key":"e_1_2_8_7_1","first-page":"289","volume":"11","author":"Severs M.","year":"2017","journal-title":"J. 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