Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Sanzo, Gakuen-cho, Fukuyama, Hiroshima, 729-0292, Japan.
Sci Rep. 2019 Mar 7;9(1):3833. doi: 10.1038/s41598-019-40278-2.
Interindividual differences affect the purgative activities of sennoside A (SA) and Daiokanzoto (Da-Huang-Gan-Cao-Tang, DKT). In this study, we manipulated gut microbiota in mice to establish laxative responders and non-responders by feeding them a high-carbohydrate, a high-fat or a high-fibre diet. To assess the relationship between laxatives and gut microbiota, we monitored the gut microbiota before and after administering laxatives. Twenty mice per diet were divided into four groups of five mice to evaluate purgative activities of four laxative preparations, DKT, SA, SA plus rhein 8-O-β-D-glucopyranoside (SA + RG), and SA plus liquiritin (SA + LQ). Gut microbiota changes were monitored by next-generation sequencing of 16 S rRNA gene amplicons. In high-carbohydrate and high-fat diet-fed mice, DKT exerted a significantly higher purgative activity than SA alone, and RG contributed to this activity. DKT and SA + RG administration increased the Enterobacteriaceae content of gut microbiota, which was associated with an increased purgative activity. In contrast, DKT activity was significantly suppressed by high-fibre diet. Hence, diet-induced differences in gut microbiota determined the effect of DKT, which is interesting, considering that Oriental medicines are formulated for a specific functional state or "pattern". These results demonstrated that the purgative activity of anthranoid laxatives is susceptible to diet-induced alterations in gut microbiota.
个体差异会影响番泻苷 A(SA)和大黃甘草湯(大黄甘草汤,DKT)的泻下作用。在这项研究中,我们通过给小鼠喂食高碳水化合物、高脂肪或高纤维饮食来操纵肠道微生物群,以建立泻药应答者和非应答者。为了评估泻药和肠道微生物群之间的关系,我们在给药前后监测肠道微生物群。每种饮食有 20 只小鼠,分为 5 只小鼠一组的四组,以评估四种泻药制剂,DKT、SA、SA 加rhein 8-O-β-D-吡喃葡萄糖苷(SA+RG)和 SA 加甘草苷(SA+LQ)的泻下活性。通过 16S rRNA 基因扩增子的下一代测序监测肠道微生物群的变化。在高碳水化合物和高脂肪饮食喂养的小鼠中,DKT 的泻下活性明显高于单独的 SA,而 RG 有助于这种活性。DKT 和 SA+RG 的给药增加了肠道微生物群的肠杆菌科含量,这与泻下活性的增加有关。相比之下,高纤维饮食显著抑制了 DKT 的活性。因此,肠道微生物群的饮食诱导差异决定了 DKT 的作用,这很有趣,因为东方药物是针对特定的功能状态或“模式”来配方的。这些结果表明,蒽醌类泻药的泻下活性易受饮食诱导的肠道微生物群变化的影响。