Jourová L, Anzenbacher P, Lišková B, Matušková Z, Hermanová P, Hudcovic T, Kozáková H, Hrnčířová L, Anzenbacherová E
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
Department of Pharmacology, Palacky University Olomouc, Olomouc, Czech Republic.
Folia Microbiol (Praha). 2017 Nov;62(6):463-469. doi: 10.1007/s12223-017-0517-8. Epub 2017 Mar 23.
Gut microbiota provides a wide range of beneficial function for the host and has an immense effect on the host's health state. It has also been shown that gut microbiome is often involved in the biotransformation of xenobiotics; however, the molecular mechanisms of the interaction between the gut bacteria and the metabolism of drugs by the host are still unclear. To investigate the effect of microbial colonization on messenger RNA (mRNA) expression of liver cytochromes P450 (CYPs), the main drug-metabolizing enzymes, we used germ-free (GF) mice, lacking the intestinal flora and mice monocolonized by non-pathogenic bacteria Lactobacillus plantarum or probiotic bacteria Escherichia coli Nissle 1917 compared to specific pathogen-free (SPF) mice. Our results show that the mRNA expression of Cyp1a2 and Cyp2e1 was significantly increased, while the expression of Cyp3a11 mRNA was decreased under GF conditions compared to the SPF mice. The both bacteria L. plantarum and E. coli Nissle 1917 given to the GF mice decreased the level of Cyp1a2 mRNA and normalized it to the control level. On the other hand, the colonization by these bacteria had no effect on the expression of Cyp3a11 mRNA in the liver of the GF mice (which remained decreased). Surprisingly, monocolonization with chosen bacterial strains has shown a different effect on the expression of Cyp2e1 mRNA in GF mice. Increased level of Cyp2e1 expression observed in the GF mice was found also in mice colonized by L. plantarum ; however, the colonization with probiotic E. coli Nissle 1917 caused a decrease in Cyp2e1 expression and partially restored the SPF mice conditions.
肠道微生物群为宿主提供了广泛的有益功能，对宿主的健康状态有巨大影响。研究还表明，肠道微生物群通常参与外源性物质的生物转化；然而，肠道细菌与宿主药物代谢之间相互作用的分子机制仍不清楚。为了研究微生物定植对肝脏细胞色素P450（CYPs，主要的药物代谢酶）信使核糖核酸（mRNA）表达的影响，我们使用了无菌（GF）小鼠（缺乏肠道菌群）、由非致病性植物乳杆菌或益生菌大肠杆菌Nissle 1917单一定植的小鼠，并与无特定病原体（SPF）小鼠进行比较。我们的结果表明，与SPF小鼠相比，在GF条件下，Cyp1a2和Cyp2e1的mRNA表达显著增加，而Cyp3a11 mRNA的表达则降低。给予GF小鼠植物乳杆菌和大肠杆菌Nissle 1917均降低了Cyp1a2 mRNA的水平，并使其恢复到对照水平。另一方面，这些细菌的定植对GF小鼠肝脏中Cyp3a11 mRNA的表达没有影响（其仍保持降低）。令人惊讶的是，用选定的细菌菌株单一定植对GF小鼠中Cyp2e1 mRNA的表达显示出不同的影响。在GF小鼠中观察到的Cyp2e1表达水平升高在植物乳杆菌定植的小鼠中也有发现；然而，用益生菌大肠杆菌Nissle 1917定植导致Cyp2e1表达降低，并部分恢复到SPF小鼠的状态。
