Wahlström Annika, Kovatcheva-Datchary Petia, Ståhlman Marcus, Bäckhed Fredrik, Marschall Hanns-Ulrich
Sahlgrenska Academy, Institute of Medicine, Department of Molecular and Clinical Medicine and Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
Dig Dis. 2017;35(3):246-250. doi: 10.1159/000450982. Epub 2017 Mar 1.
The gut microbiota has a substantial impact on health and disease. The human gut microbiota influences the development and progression of metabolic diseases; however, the underlying mechanisms are not fully understood. The nuclear farnesoid X receptor (FXR), which regulates bile acid homeostasis and glucose and lipid metabolism, is activated by primary human and murine bile acids, chenodeoxycholic acid and cholic acid, while rodent specific primary bile acids tauromuricholic acids antagonise FXR activation. The gut microbiota deconjugates and subsequently metabolises primary bile acids into secondary bile acids in the gut and thereby changes FXR activation and signalling. Key Message: Mouse models have been used to study the crosstalk between bile acids and the gut microbiota, but the substantial differences in bile acid composition between humans and mice need to be considered when interpreting data from such studies and for the development of so-called humanised mouse models.
It is of special importance to elucidate how a human gut microbiota influences bile acid composition and FXR signalling in colonised mice.
肠道微生物群对健康和疾病有重大影响。人类肠道微生物群影响代谢性疾病的发生和发展;然而,其潜在机制尚未完全明确。核法尼醇X受体(FXR)可调节胆汁酸稳态以及葡萄糖和脂质代谢,被人和小鼠的初级胆汁酸鹅去氧胆酸和胆酸激活,而啮齿动物特有的初级胆汁酸牛磺鼠胆酸则拮抗FXR的激活。肠道微生物群使初级胆汁酸去结合,并随后在肠道中将其代谢为次级胆汁酸,从而改变FXR的激活和信号传导。关键信息:小鼠模型已被用于研究胆汁酸与肠道微生物群之间的相互作用,但在解释此类研究的数据以及开发所谓的人源化小鼠模型时,需要考虑人类和小鼠胆汁酸组成的显著差异。
阐明人类肠道微生物群如何影响定殖小鼠的胆汁酸组成和FXR信号传导尤为重要。