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This study investigated WGPII effects in cyclophosphamide (CTX)-induced intestinal injury mice. WGPII significantly reversed immunosuppression by increasing serum cytokines and immunoglobulins and mitigated intestinal damage by upregulating SIgA and tight junction proteins. 16S rDNA sequencing and metabolomics revealed that WGPII enriched beneficial taxa (Lachnospiraceae_NK4A136_group, Roseburia) and decreased Bacteroides, correlating with TCA cycle activation and key metabolite enrichment (\u03b1-ketoglutarate, pyruvate, and N-acetyl-l-glutamate). WGPII also upregulated colonic miR-217-5p, miR-769-x, and miR-654-3p, while suppressing their predicted targets (Cxcl12, Mapk4, IL-17F). Correlation analysis suggested a potential \u201cmiRNA-gut microbiota-metabolite\u201d regulatory network that may contribute to WGPII\u2019s protective effects. These correlational findings provide a theoretical basis for developing WGPII-based functional products for intestinal health, though direct mechanistic validation is warranted.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05499","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:04:28Z","timestamp":1785949468000},"page":"25300-25314","source":"Crossref","is-referenced-by-count":0,"title":["Wheat Germ Glycoprotein\n(WGPII) Alleviates Cyclophosphamide-Induced\nIntestinal Injury: Integrative Multiomics Reveals a Potential miRNA-Gut\nMicrobiota-Metabolite Regulatory Network"],"prefix":"10.1021","volume":"74","author":[{"given":"Jinpeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Agricultural University , , ,","place":["Tianjin, China, 300392"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Agricultural University , , ,","place":["Tianjin, China, 300392"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Agricultural University , , ,","place":["Tianjin, China, 300392"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiran","family":"Xu","sequence":"additional","affiliation":[{"name":"Tianjin Agricultural University , , ,","place":["Tianjin, China, 300392"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4030-1425","authenticated-orcid":true,"given":"Liyuan","family":"Yun","sequence":"additional","affiliation":[{"name":"Tianjin Agricultural University , , ,","place":["Tianjin, China, 300392"]},{"name":"Key Laboratory of Smart Breeding(Co-Constructionby Ministry and Province), Ministry of Agriculture and RuralAffairs , ,","place":["Tianjin, China, 300392"]},{"name":"Tianjin Key Laboratory of Intelligent Breeding of Major Crops , ,","place":["Tianjin, China, 300392"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalita","family":"Siriwattananon","sequence":"additional","affiliation":[{"name":"Tianjin Agricultural University Nutritious and Healthy FoodSino-Thailand Joint Research Center , ,","place":["Tianjin, China, 300392"]},{"name":"Rajamangala University of Technology Thanyaburi , , ,","place":["Khlong Hok, Thailand, 12130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-4002","authenticated-orcid":true,"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Agricultural University , , ,","place":["Tianjin, China, 300392"]},{"name":"Key Laboratory of Smart Breeding(Co-Constructionby Ministry and Province), Ministry of Agriculture and RuralAffairs , ,","place":["Tianjin, China, 300392"]},{"name":"Tianjin Key Laboratory of Intelligent Breeding of Major Crops , ,","place":["Tianjin, China, 300392"]},{"name":"Tianjin Agricultural University Nutritious and Healthy FoodSino-Thailand Joint Research Center , ,","place":["Tianjin, China, 300392"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"10","key":"2026081910185375800_cit1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8101587","article-title":"Gut Microbiota\nand Immune System Interactions","volume":"8","author":"Yoo","year":"2020","journal-title":"Microorganisms"},{"issue":"1","key":"2026081910185375800_cit2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41577-022-00727-y","article-title":"The impact\nof the gut microbiome on extra-intestinal autoimmune diseases","volume":"23","author":"Miyauchi","year":"2023","journal-title":"Nat. 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