{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:41:56Z","timestamp":1792464116620,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central Government in Guidance of Local Science and Technology Development of the Xizang Autonomous Region, China","award":["XZ202401YD0010"],"award-info":[{"award-number":["XZ202401YD0010"]}]},{"name":"Xizang Autonomous Region, China","award":["XZ202501JD0007"],"award-info":[{"award-number":["XZ202501JD0007"]}]},{"name":"Xizang Autonomous Region, China","award":["XZ202502YD0002"],"award-info":[{"award-number":["XZ202502YD0002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is implicated in the pathogenesis of ulcerative colitis (UC). Tryptophan metabolism and its interaction with the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2\u2013related factor 2 (Nrf2) axis represent a crucial regulatory network in intestinal homeostasis. This study aimed to investigate whether the probiotic fermentation product postbiotic Nagqu4580 alleviates UC by modulating this network to inhibit intestinal epithelial ferroptosis. Methods: An acute UC model was induced in mice using 4% dextran sodium sulfate (DSS). The therapeutic effects of postbiotic Nagqu4580 were evaluated through disease activity index (DAI), colon length, histopathology, inflammatory cytokines, and intestinal barrier function. Ferroptosis was assessed by measuring lipid peroxidation (MDA, 4-HNE), antioxidant capacity (GSH\/GSSG), and expression levels of GPX4 and ACSL4. Serum tryptophan metabolites were profiled using targeted metabolomics, the activation of the AhR\/Nrf2 pathway was examined by Western blot, immunofluorescence, and qPCR, and gut microbiota composition was analyzed by 16S rRNA sequencing. Results: Postbiotic Nagqu4580 dose-dependently ameliorated DSS-induced UC in mice, as evidenced by reduced DAI scores, mitigated colon shortening and histological damage, decreased inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6), and restored intestinal barrier function by upregulating tight junction proteins (Claudin-1, ZO-1, Occludin). Mechanistically, postbiotic Nagqu4580 inhibited intestinal epithelial ferroptosis by reducing MDA and 4-HNE levels, restoring the GSH\/GSSG balance, downregulating ACSL4, and upregulating GPX4. Serum metabolomics revealed that postbiotic Nagqu4580 reshaped tryptophan metabolism, increasing beneficial metabolites such as 5-hydroxyindoleacetic acid (5-HIAA) and decreasing potentially harmful metabolites such as 3-indoxyl sulfate (3-IS). 16S rRNA sequencing further revealed that the postbiotic Nagqu4580 partially reversed DSS-induced gut microbiota dysbiosis, with a slight increase in the abundance of beneficial genera and a significant reduction in the abundance of pro-inflammatory genera. Furthermore, postbiotic Nagqu4580 significantly activated the AhR\/Nrf2 signaling pathway, enhancing the expression of AhR, Nrf2, and their downstream antioxidant genes HO-1 and GPX4. Conclusions: Postbiotic Nagqu4580 alleviates UC by inhibiting intestinal epithelial ferroptosis. Our data suggest that this protective effect is associated with the remodeling of gut microbiota-related tryptophan metabolism and subsequent activation of the AhR\/Nrf2 antioxidant axis. Our findings highlight the therapeutic potential of postbiotic Nagqu4580 as a postbiotic agent for UC.<\/jats:p>","DOI":"10.3390\/nu18132150","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:25Z","timestamp":1783003885000},"page":"2150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Postbiotic Nagqu4580 Attenuates Ulcerative Colitis and Suppresses Ferroptosis in Association with the Microbiota-Tryptophan-AhR\/Nrf2 Axis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6270-7712","authenticated-orcid":false,"given":"Xiangjun","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"},{"name":"Clinical Medical Research Center for Plateau Gastroenterological Disease of Xizang Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1913-7989","authenticated-orcid":false,"given":"Zhengyang","family":"Hao","sequence":"additional","affiliation":[{"name":"Clinical Medical Research Center for Plateau Gastroenterological Disease of Xizang Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruipeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"},{"name":"Clinical Medical Research Center for Plateau Gastroenterological Disease of Xizang Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Tu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-7655","authenticated-orcid":false,"given":"Shaokang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"},{"name":"Clinical Medical Research Center for Plateau Gastroenterological Disease of Xizang Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5969-2185","authenticated-orcid":false,"given":"Guiju","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2263210","DOI":"10.1080\/19490976.2023.2263210","article-title":"The Influence of Microbiota on Ferroptosis in Intestinal Diseases","volume":"15","author":"Yao","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gao, S., Sun, C., and Kong, J. 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