Combined metabolomics and gut microbiota analysis reveals the protective effects of α-monoglucosyl rutin against cyclophosphamide-induced intestinal injury

α-Monoglucosyl rutin (α-GR) is a structurally optimized rutin derivative, and its higher water solubility and bioavailability may help it exert better pharmacological effects in vivo . The present study examined the protective effects and potential mechanisms of α-GR on cyclophosphamide (CTX)-induced colonic injury in mice. The findings showed that α-GR significantly reduced serum levels of lipopolysaccharide (LPS) and diamine oxidase (DAO), effectively alleviating the histopathological damage in colon tissues caused by CTX exposure. Additionally, α-GR maintained the integrity of intestinal epithelial cells by promoting the secretion of secretory immunoglobulin A (sIgA) and upregulating the expression of tight junction proteins (Claudin-1 and ZO-1), while also reducing the levels of colonic pro-inflammatory factors and oxidative stress. In terms of gut microbiota, 16S rRNA gene sequencing and metabolomic analyses revealed that α-GR could effectively reverse the gut metabolic disorders and microbiota structural changes induced by CTX, promoted the growth of beneficial bacteria like norank_f_Muribaculaceae , Bacteroides, and Alloprevotella , and reduced the relative abundance of pathogenic bacteria ( Desulfovibrio ), while also revealing the complex correlation between them. In terms of mechanism research, α-GR further attenuated intestinal damage by regulating the TLR4/NF-κB and Nrf2/HO-1 pathways. This provides new ideas for the development of functional dietary supplements to treat CTX-associated intestinal toxicity.