Watanabe Masamichi, Fukiya Satoru, Yokota Atsushi
Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido 060-8589, Japan.
Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido 060-8589, Japan
J Lipid Res. 2017 Jun;58(6):1143-1152. doi: 10.1194/jlr.M075143. Epub 2017 Apr 12.
In addition to functioning as detergents that aid digestion of dietary lipids in the intestine, some bile acids have been shown to exhibit antimicrobial activity. However, detailed information on the bactericidal activities of the diverse molecular species of bile acid in humans and rodents is largely unknown. Here, we investigated the toxicity of 14 typical human and rodent free bile acids (FBAs) by monitoring intracellular pH, membrane integrity, and viability of a human intestinal bacterium, Japan Collection of Microorganisms (JCM) 1192, upon exposure to these FBAs. Of all FBAs evaluated, deoxycholic acid (DCA) and chenodeoxycholic acid displayed the highest toxicities. Nine FBAs common to humans and rodents demonstrated that α-hydroxy-type bile acids are more toxic than their oxo-derivatives and β-hydroxy-type epimers. In five rodent-specific FBAs, β-muricholic acid and hyodeoxycholic acid showed comparable toxicities at a level close to DCA. Similar trends were observed for the membrane-damaging effects and bactericidal activities to JCM 1395 and DSM 2079, commonly represented in the human and rodent gut microbiota. These findings will help us to determine the fundamental properties of FBAs and better understand the role of FBAs in the regulation of gut microbiota composition.
除了作为有助于肠道中膳食脂质消化的去污剂发挥作用外，一些胆汁酸还显示出抗菌活性。然而，关于人类和啮齿动物中不同分子种类胆汁酸的杀菌活性的详细信息在很大程度上尚不清楚。在这里，我们通过监测人肠道细菌日本微生物保藏中心（JCM）1192在暴露于这些游离胆汁酸（FBAs）时的细胞内pH值、膜完整性和活力，研究了14种典型的人和啮齿动物游离胆汁酸的毒性。在所有评估的FBA中，脱氧胆酸（DCA）和鹅去氧胆酸表现出最高的毒性。人和啮齿动物共有的9种FBA表明，α-羟基型胆汁酸比其氧代衍生物和β-羟基型差向异构体毒性更大。在5种啮齿动物特有的FBA中，β-鼠胆酸和猪去氧胆酸在接近DCA的水平上表现出相当的毒性。对于人类和啮齿动物肠道微生物群中常见的JCM 1395和DSM 2079，在膜损伤作用和杀菌活性方面也观察到了类似的趋势。这些发现将有助于我们确定FBA的基本特性，并更好地理解FBA在调节肠道微生物群组成中的作用。
