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Aiming to provide additional insights into disease development and potential treatment strategies, the present study investigates the local effect of oral treatment with polysaccharides obtained from Auricularia auricula\u2019s submerged culture in an experimental model of DSS-induced colitis and its impact on lesion resolution. Methods: The structure and monosaccharide composition of Auricularia polysaccharides were characterized through Nuclear Magnetic Resonance (NMR). To evaluate the effect of this polysaccharide on the murine model, wild-type and Dectin-1 knockout mice were treated or not with the exopolysaccharide (EPS) while under DSS consumption. During the experimental period, feces samples were collected to evaluate microbial shifts during disease development, and, finally, the colonic tissue was analyzed to assess the inflammatory process and cytokine production. Results: The EPS composition showed a polymeric mixture of glucans and fucogalactomannans. The treatment of the wild-type DSS-induced colitis group improved the inflammatory response by increasing gut\u2013homeostatic cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-\u03b1). The Dectin-1 KO mice group did not show the same enhancement after EPS treatment. The microbiome analysis revealed a difference in the genotype, and the treatment modified the DSS microbiome modulation, with nine and four ASVs in WT and Dectin-1 KO mice, respectively. Conclusions: The EPS treatment demonstrated therapeutic potential in treating inflammatory intestinal diseases by modulating cytokine secretion and microbiota composition, which is dependent on the Dectin-1 receptor\u2019s carbohydrate recognition.<\/jats:p>","DOI":"10.3390\/ph18081085","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:00:42Z","timestamp":1753196442000},"page":"1085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Auricularia auricula\u2019s Exopolysaccharide Mitigates DSS-Induced Colitis Through Dectin\u20131-Mediated Immunomodulation and Microbiota Remodeling"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2395-7748","authenticated-orcid":false,"given":"Lu\u00edsa Coutinho","family":"Coelho","sequence":"first","affiliation":[{"name":"Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Federal District, Brasilia 70910-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edsa Dan","family":"Favilla","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Federal District, Brasilia 70910-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais Bergmann","family":"de Castro","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Federal District, Brasilia 70910-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5474-9728","authenticated-orcid":false,"given":"Maria Carolina B. Di Medeiros","family":"Leal","sequence":"additional","affiliation":[{"name":"Medicine Department, University Center of Planalto Central Aparecido dos Santos, Federal District, Brasilia 72445-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3323-5300","authenticated-orcid":false,"given":"Anam\u00e9lia Lorenzetti","family":"Bocca","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasilia, Federal District, Brasilia 70910-000, Brazil"},{"name":"Bi-Institutional Translational Medicine Platform, Oswaldo Cruz Foundation (Fiocruz), Ribeir\u00e3o Preto 14049900, S\u00e3o Paulo, Brazil"},{"name":"National Institute of Science and Technology in Human Pathogenic Fungi, Ribeir\u00e3o Preto 14049900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhu, K., Zeng, S., Zheng, Y., Cao, J., and Li, C. 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