{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:14:14Z","timestamp":1789456454504,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":256,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>This study employs a multiomics approach to investigate the protective effects of fucoxanthin (Fu) and explore its potential association with metabolic and signaling pathways in diabetic mice induced by a high\u2010fat diet combined with streptozotocin (STZ) administration. Diabetic model mice were randomly divided into normal control (NC), diabetic model, low\u2010dose Fu (50\u2009mg\/kg\/day), and high\u2010dose Fu (100\u2009mg\/kg\/day) groups. After 6 weeks of intervention, Fu treatment was associated with dose\u2010dependent improvements in glucose and lipid metabolism, reduced oxidative stress, decreased expression of inflammatory cytokines (tumor necrosis factor\u2010\u03b1 [TNF\u2010\u03b1], interleukin\u20106 [IL\u20106], and IL\u20101\u03b2) and renal fibrosis markers (TGF\u2010\u03b21, \u03b1\u2010SMA, and Col1a1), along with notable attenuation of renal pathological damage. Exploratory analyses indicated that these phenotypic improvements were accompanied by reduced renal IDO1 expression, favorable shifts in tryptophan (Trp) metabolism, and upregulated AhR\/CYP1A1 signaling. 16S rRNA sequencing revealed that Fu treatment was associated with a restoration of diabetes\u2010altered gut microbiota \u03b2\u2010diversity. Serum metabolomics identified that Fu administration correlated with alterations in multiple metabolites (including 5\u2032\u2010S\u2010methyl\u20105\u2032\u2010thioadenosine, LPC 16:0, and bile acids), which are linked to key pathways such as Trp metabolism and bile acid biosynthesis. Network pharmacology predictions further suggested potential multitarget interactions of Fu with the PI3K\u2010Akt and AGE\u2010RAGE signaling pathways. Collectively, these findings indicate that Fu exerts potential renoprotective effects in diabetic mice, which are accompanied by a normalization of Trp\u2013AhR pathway\u2010related metabolism and concurrent attenuation of inflammatory, oxidative, and fibrotic responses. While causal functional links remain to be fully elucidated, these observations provide a preliminary basis for further mechanistic investigation and support the potential of Fu as a dietary supplement or adjunctive strategy for diabetic kidney disease (DKD).<\/jats:p>","DOI":"10.1155\/jimr\/1020462","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:53:17Z","timestamp":1789455197000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fucoxanthin Ameliorates Diabetic Kidney Disease via Modulating the Gut Microbiota and Tryptophan\u2013Kynurenine Metabolic Pathway"],"prefix":"10.1155","volume":"2026","author":[{"given":"Donglin","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5945-9923","authenticated-orcid":false,"given":"Jiayong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2724-9033","authenticated-orcid":false,"given":"Xueyun","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3252-8403","authenticated-orcid":false,"given":"Hao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2416-8211","authenticated-orcid":false,"given":"Yunhan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3357-710X","authenticated-orcid":false,"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0100-1692","authenticated-orcid":false,"given":"Linlin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-5085","authenticated-orcid":false,"given":"Asmaa","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3240-3967","authenticated-orcid":false,"given":"Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-2368","authenticated-orcid":false,"given":"Leilei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5023-926X","authenticated-orcid":false,"given":"Jiayuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-2433","authenticated-orcid":false,"given":"Liang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1537-1271","authenticated-orcid":false,"given":"Keke","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9841-8_1"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1185317"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2017.12.002"},{"key":"e_1_2_12_4_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/dom.14007","article-title":"An Updated Overview of Diabetic Nephropathy: Diagnosis, Prognosis, Treatment Goals and Latest Guidelines","volume":"22","author":"Selby N. M.","year":"2020","journal-title":"Diabetes, Obesity and Metabolism"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2018.9"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad190"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2025.2517402"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065742"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/723515"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2010.05.006"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/8810106"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/1222395"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27248715"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000035397"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20143393"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06257-5"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells4040631"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2023.2165103"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154915"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107117"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2025.1492499"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-1147"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-021-00329-w"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.003"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.782199"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116176"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1032208"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323071"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05249-7"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24661"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0258-z"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.158"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0029-9"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1207132"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2019-0657"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu14061128"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12050389"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2011.04244.x"},{"key":"e_1_2_12_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph18071061"},{"key":"e_1_2_12_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11070453"},{"key":"e_1_2_12_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27196221"},{"key":"e_1_2_12_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003012"},{"key":"e_1_2_12_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/biof.2079"},{"key":"e_1_2_12_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1276217"},{"key":"e_1_2_12_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.991059"},{"key":"e_1_2_12_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.119158"},{"key":"e_1_2_12_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26189107"},{"key":"e_1_2_12_49_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.3904"},{"key":"e_1_2_12_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-021-00429-z"},{"key":"e_1_2_12_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu13072306"},{"key":"e_1_2_12_52_2","article-title":"Human Gut Microbiome Modulation and Butyrogenic Effects of Fucoidan From Sargassum Binderi: A Prebiotic Activity in In Vitro Simulated Digestion and Human Fecal Fermentation","volume":"15","author":"Nattha T.","year":"2025","journal-title":"International Journal of Biological Macromolecules"},{"key":"e_1_2_12_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-023-03256-z"},{"key":"e_1_2_12_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-021-02509-z"},{"key":"e_1_2_12_55_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098203"},{"key":"e_1_2_12_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01913-1"},{"key":"e_1_2_12_57_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2022.2142194"},{"key":"e_1_2_12_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101841"},{"key":"e_1_2_12_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202300734"},{"key":"e_1_2_12_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1661037"},{"key":"e_1_2_12_61_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S530823"}],"container-title":["Journal of Immunology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jimr\/1020462","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/jimr\/1020462","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jimr\/1020462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:53:19Z","timestamp":1789455199000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/jimr\/1020462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":61,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/jimr\/1020462"],"URL":"https:\/\/doi.org\/10.1155\/jimr\/1020462","archive":["Portico"],"relation":{},"ISSN":["2314-8861","2314-7156"],"issn-type":[{"value":"2314-8861","type":"print"},{"value":"2314-7156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1020462"}}