Dietary tangeretin improved antibiotic-associated diarrhea in mice by enhancing the intestinal barrier function, regulating the gut microbiota, and metabolic homeostasis.

Antibiotic-associated diarrhea is mediated by antibiotic treatment and is usually caused by the disruption of the intestinal barrier, gut microbiota, and metabolic balance. To identify a dietary strategy that can mitigate the side effects of antibiotics, this study investigated the effect of tangeretin on antibiotic-associated diarrhea in C57BL/6 mice. The results revealed that dietary tangeretin significantly ameliorated symptoms of antibiotic-associated diarrhea, as evidenced by the decreased diarrhea status scores, the reduced fecal water content, the decreased caecum/body weight ratio, and the alleviated colonic tissue damage. Dietary tangeretin also exhibited a protective effect on the intestinal barrier function by upregulating the mRNA and protein expression of claudin-1 and ZO-1. Furthermore, analysis of the gut microbiota using 16S rRNA gene sequencing indicated that dietary tangeretin modulated the gut microbiota of mice with antibiotic-associated diarrhea via increasing the gut microbiota diversity and the abundance of beneficial bacteria, e.g. , Lactobacillaceae and Ruminococcaceae , and decreasing the abundance of harmful bacteria, e.g. , Enterococcus and Terrisporobacter . Additionally, dietary tangeretin restored the levels of short-chain fatty acids and modulated metabolic pathways by enriching purine metabolism, bile acid metabolism, ABC transporters, and choline metabolism in cancer. Collectively, these findings provide a solid scientific basis for the rational use of tangeretin as a preventive and therapeutic agent for antibiotic-associated diarrhea.