探讨牛乳低聚糖改善抗生素相关腹泻的效果。氨苄西林诱导C57BL/6J小鼠建立抗生素相关腹泻模型,小鼠分为正常对照组,模型组和牛乳低聚糖低、高剂量组,干预一周后,分析小鼠腹泻表型、炎症因子水平和紧密连接蛋白表达水平,通过16S rRNA高通量测序和气相色谱分析肠道菌群及短链脂肪酸代谢。结果显示,与模型组相比,牛乳低聚糖高剂量组小鼠体重、AQP3和AQP4分别增加了8.65%、128.46%和12.86%,粪便含水率降低24.51%,血清中IL-6、TNF-α和IL-1β降低了26.98%、30.31%和37.60%,IL-10和INF-γ增加了59.21%和27.16,显著增加了紧密连接蛋白ZO-1、Claudin-1和Occludin。牛乳低聚糖高剂量组富集了阿克曼菌、拟杆菌、副拟杆菌属和杜伯氏菌,恢复了肠道菌群的平衡。牛乳低聚糖高剂量组还促进了小鼠肠道内乙酸、丙酸和丁酸的生成。综上,牛乳低聚糖通过改善小鼠腹泻表型、调节肠道炎症反应、促进肠道屏障功能、富集有益菌群,展现出改善抗生素相关腹泻的作用。

The aim of this study was to investigate the effect of milk oligosaccharides on alleviating antibiotic-associated diarrhea. An antibiotic-associated diarrhea model was established in C57BL/6J mice through ampicillin induction. The mice were randomly divided into a normal control group, a model group, and low- and high-dose milk oligosaccharide groups. After one week of intervention, the diarrhea phenotype, inflammatory cytokine levels, tight junction protein expression, intestinal microbiota, and short-chain fatty acid metabolism were analyzed using 16S rRNA high-throughput sequencing and gas chromatography. The results showed that, compared to the model group, the body weight, AQP3, and AQP4 levels in the high-dose milk oligosaccharide group increased by 8.65%, 128.46%, and 12.86%, respectively. The fecal moisture content decreased by 24.51%, while the levels of IL-6, TNF-α, and IL-1β were reduced by 26.98%, 30.31%, and 37.60%, respectively. In contrast, the levels of IL-10 and IFN-γ were increased by 59.21% and 27.16%, and the expression of tight junction proteins ZO-1, Claudin-1, and Occludin was significantly upregulated. The high-dose milk oligosaccharide group enriched Akkermansia, Bacteroidetes, Parabacteroides, and Duberella, thereby restoring the balance of intestinal microbiota. Additionally, the high-dose milk oligosaccharide group promoted the production of acetic acid, propionic acid, and butyric acid in the intestines of the mice. In summary, milk oligosaccharides can ameliorate antibiotic-associated diarrhea by improving the diarrhea phenotype, regulating the intestinal inflammatory response, promoting intestinal barrier function, and enriching beneficial microbiota.

哈尔滨学院青年博士科研启动基金项目 （HUDF2021113）