Abstract: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.
