Effects of Compound Probiotics on Pharmacokinetics of Cytochrome 450 Probe Drugs in Rats

• DOI: 10.1124/dmd.124.001837
• Publication Date: 2024-08-30T16:45:12Z
• Authors: Yanjuan Zhang; Zhi Chen; Yayi Xiao; Tianyuan Wu; Haijun Yang; Yujie Liu; Rong Zhou; Yalan Xiong; Yanling Xiong; Xuechun Yang; Jian Zhou; Honghao Zhou; Wei Zhang; Yan Shu; Xiong Li; Fugang Guo; Jianhui Yin; Shang Liao; Qing Li; Peng Zhu
• Keywords: Male; Bile Acids and Salts; Jejunum; Cytochrome P-450 Enzyme System; Liver; Probiotics; Animals; Biological Availability; Rats, Wistar; Rats; Gastrointestinal Microbiome

Compound probiotics have been widely used and commonly co-administered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 metabolism probe cytochrome P450 enzymes (CYP450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin chlorzoxazone. Male Wistar rats were administered drinking water containing or not 14 days then intragastrically a CYP450s cocktail; was done to investigate host metabolic phenotype. Stool, liver/jejunum serum samples collected 16S rRNA sequencing, RNA bile acid profiling. The results indicated significant differences in both alpha beta diversity intestinal microbial composition between probiotic vehicle groups rats. In group, bioavailability omeprazole increased by 269.9%, whereas those tolbutamide chlorpropamide decreased 28.1% 27.4%, respectively. liver jejunum exhibited 1,417 4,004 differentially expressed genes, respectively, two groups. most genes upregulated but downregulated jejunum. expression encoding transporters also changed. conjugated acids group significantly reduced. Shorter duodenal villi longer ileal found group. summary, administration altered gut microbiota, drug-processing gene expression, structure rats, which could be reasons pharmacokinetic changes. <b>Significance Statement</b> focused profile genes. Compared previous studies, current provides comprehensive explanation modified probiotics, here combined histopathological analysis.