%0 Journal Article %A Chong Ma %A Ying Guo %A Curtis D. Klaassen %T Effect of Gender and Various Diets on Bile Acid Profile and Related Genes in Mice %D 2021 %R 10.1124/dmd.120.000166 %J Drug Metabolism and Disposition %P 62-71 %V 49 %N 1 %X Diet is an important factor for many diseases. Previous studies have demonstrated that several diets had remarkable effects on bile acid (BA) homeostasis, but no comprehensive information for both genders has been reported. Therefore, the current study characterized the nine most used laboratory animal diets fed to both genders of mice for a comparable evaluation of the topic. The results revealed that marked gender difference of BA homeostasis is ubiquitous in mice fed the various diets, and of the nine diets fed to mice, the atherogenic and calorie-restricted diets had the most marked effects on BA homeostasis, followed by the laboratory chow and essential fatty acid–deficient diets. More specifically, females had higher concentrations of total BAs in serum when fed six of the nine diets compared with male mice, and 26 of the 35 BA-related genes had marked gender difference in mice fed at least one diet. Although mice fed the calorie-restricted and atherogenic diets had increased BA, which was more pronounced in serum than liver, the intestinal farnesoid X nuclear receptor–fibroblast growth factor 15 axis changed in the opposite direction and resulted in different hepatic expression patterns of Cyp7a1. Compared with AIN-93M purified diet, higher hepatic expression of multidrug resistance–associated protein 3 was the only alteration in mice fed the laboratory chow diet. The other diets had little or no effect on BA concentrations in the liver and plasma or in the expression of BA-related genes. This study indicates that gender, the atherogenic diet, and the calorie-restricted diet have the most marked effects on BA homeostasis.SIGNIFICANCE STATEMENT Previous evidence suggested that various diets have effect on bile acid (BA) homeostasis; however, it is not possible to directly compare these findings, as they are all from different studies. The current study was the first to systematically investigate the influence of the nine most used experimental mouse diets on BA homeostasis and potential mechanism in both genders of mice and indicates that gender, the atherogenic diet, and the calorie-restricted diet have the most marked effects on BA homeostasis, which will aid future investigations. %U https://dmd.aspetjournals.org/content/dmd/49/1/62.full.pdf