Huarong Xu

5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is a dose-limiting complication of chemotherapy that severely compromises patient quality of life and treatment adherence. Coix seed (CS), a traditional cereal grain with established “medicine food homology” status in East Asia, has demonstrated potential benefits for intestinal health. However, the protective mechanisms of this functional food against chemotherapy-induced gastrointestinal toxicity remain unexplored. Here, we demonstrate for the first time that dietary CS supplementation effectively alleviates 5-FU-induced IM without compromising antitumor efficacy. Integrated 16S rDNA sequencing revealed that CS ameliorated 5-FU-induced gut microbiota dysbiosis by suppressing pathogenic bacteria while enriching beneficial commensals. Transcriptomic analysis identified the PI3K/Akt-NF-κB pathway as the key inflammatory cascade inhibited by CS. Notably, untargeted metabolomics demonstrated that CS promoted the accumulation of gut microbiota-derived inosine, a postbiotic purine metabolite. In vitro anaerobic fermentation confirmed that CS serves as a fermentable substrate for beneficial bacteria to produce inosine. Importantly, exogenous inosine administration recapitulated the gastroprotective effects of CS by suppressing PI3K/Akt-NF-κB-mediated inflammation through adenosine A₁ receptor activation. These findings establish a novel “diet-microbiota-metabolite-health” axis linking dietary CS intake to intestinal protection, providing scientific evidence for developing microbiota-targeted functional foods for the nutritional management of chemotherapy-induced IM.

The excessive expression of reactive oxygen species is closely connected to many diseases. Considerable studies have demonstrated dandelion as well as its ingredients exhibited antioxidant activity. However, specific material basis reflecting the antioxidant activity has not been comprehensively investigated. In this study, a spectrum–effect relationship study on dandelion between fingerprinting and antioxidant activity was analyzed in detail, while a UHPLC quantification method developed and completely validated for simultaneous determination of active ingredients in dandelion. With the establishment of dandelion fingerprints of different regions, 24 common peaks were characterized. The classic FRAP method and ABTS methods were then used to detect their antioxidant activity. Partial least squares regression analysis, bivariate correlation analysis and grey correlation method were used to accomplish the spectrum–effect relationship. Eventually, the ingredients with antioxidant activity which could be considered as candidate quality markers of dandelion were discovered through spectrum–effect relationship analysis. The six compounds including caftaric acid, chlorogenic acid, caffeic acid, chicoric acid, isochlorogenic acid A, and isochlorogenic acid C were quantitatively determined. The developed UHPLC assay method was accurate, precise, and reliable. The study has elucidated the antioxidant material basis of dandelion and provided a scientific basis for the quality control of dandelion.