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Gut microbiota homeostasis is necessary to maintain the healthy state of humans. MR2938, a quinazolin-4(3H)-one derivative derived from the marine natural product penipanoid C, alleviated DSS-induced colitis in a dose-dependent manner. Herein, we aimed to investigate the impact of MR2938 on the gut microbiota in dextran sodium sulfate (DSS)-induced colitis in mice and to elucidate the role of the gut microbiota in the therapeutic mechanism of MR2938 for alleviating colitis. Methods: Acute colitis was induced with DSS in mice. Mice were administered with 100 mg\/kg or 50 mg\/kg of MR2938. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following 16S RNA sequencing. Antibiotic cocktail-induced microbiome depletion was performed to further investigate the relationship between MR2938 and gut microbiota. The inflammatory factor levels were performed by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Alcian blue staining and immunofluorescence were used to estimate the intestinal barrier. Results: The 16S rRNA sequencing revealed microbiota modulation by MR2938. Compared with the model group, the 100 mg\/kg MR2938 group was associated with higher abundances of Entercoccus and a lower abundance of Staphylococcus, while the 50 mg\/kg MR2938 group was associated with higher abundances of Lactobacillus and a lower abundance of Staphylococcus. The antibiotic-mediated microbiota depletion experiments demonstrated that the gut microbiota primarily contributed to barrier function protection, with little impact on inflammatory factor levels during the MR2938 treatment. Conclusions: These findings suggest that intestinal flora play a crucial role in MR2938\u2019s therapeutic mechanism for alleviating colitis.<\/jats:p>","DOI":"10.3390\/ph18010123","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T10:27:58Z","timestamp":1737109678000},"page":"123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota"],"prefix":"10.3390","volume":"18","author":[{"given":"Ling","family":"Lv","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireguli","family":"Maimaitiming","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jichen","family":"Yang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuli","family":"Xia","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0368-5070","authenticated-orcid":false,"given":"Pingyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0266-6677","authenticated-orcid":false,"given":"Zhiqing","family":"Liu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Honap","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41586-019-1237-9","article-title":"Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases","volume":"569","author":"Arze","year":"2019","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/ibd.21509","article-title":"Characterization of Escherichia coli isolated from gut biopsies of newly diagnosed patients with inflammatory bowel disease","volume":"17","author":"Sepehri","year":"2011","journal-title":"Inflamm. 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