Wahlström Annika, Kovatcheva-Datchary Petia, Ståhlman Marcus, Khan Muhammad-Tanweer, Bäckhed Fredrik, Marschall Hanns-Ulrich
Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Molecular and Clinical Medicine and Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
J Lipid Res. 2017 Feb;58(2):412-419. doi: 10.1194/jlr.M072819. Epub 2016 Dec 12.
The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study, we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR signaling in colonized mice. We colonized germ-free mice with cecal content from a mouse donor or feces from a human donor and euthanized the mice after short-term (2 weeks) or long-term (15 weeks) colonization. We analyzed the gut microbiota and BA composition and expression of FXR target genes in ileum and liver. We found that cecal microbiota composition differed between mice colonized with mouse and human microbiota and was stable over time. Human and mouse microbiota reduced total BA levels similarly, but the humanized mice produced less secondary BAs. The human microbiota was able to reduce the levels of tauro-β-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized with a mouse microbiota.
肠道微生物群部分通过胆汁酸（BAs）的代谢以及通过法尼醇X受体（FXR）的信号转导修饰来影响代谢性疾病的发生和发展。在本研究中，我们旨在确定人类肠道微生物群如何代谢小鼠胆汁酸并影响定殖小鼠中的FXR信号传导。我们用来自小鼠供体的盲肠内容物或来自人类供体的粪便对无菌小鼠进行定殖，并在短期（2周）或长期（15周）定殖后对小鼠实施安乐死。我们分析了肠道微生物群、胆汁酸组成以及回肠和肝脏中FXR靶基因的表达。我们发现，用小鼠和人类微生物群定殖的小鼠之间盲肠微生物群组成不同，并且随时间保持稳定。人类和小鼠微生物群对总胆汁酸水平的降低作用相似，但人源化小鼠产生的次级胆汁酸较少。长期定殖后，人类微生物群能够降低牛磺-β-鼠胆酸水平，并诱导回肠中FXR靶基因Fgf15和Shp的表达。我们表明，人类微生物群可以改变定殖小鼠中的胆汁酸组成并诱导FXR信号传导，但产生的次级胆汁酸水平低于用小鼠微生物群定殖的小鼠。
