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

Abstract

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.