Wheat Germ Glycoprotein (WGPII) Alleviates Cyclophosphamide-Induced Intestinal Injury: Integrative Multiomics Reveals a Potential miRNA-Gut Microbiota-Metabolite Regulatory Network.

Wheat germ glycoprotein (WGPII) exhibits immunomodulatory activity; however, its protective mechanisms against intestinal injury remain unclear. 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 (α-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 "miRNA-gut microbiota-metabolite" regulatory network that may contribute to WGPII's protective effects. These correlational findings provide a theoretical basis for developing WGPII-based functional products for intestinal health, though direct mechanistic validation is warranted.