Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota

TY - JOUR

T1 - Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota

AU - Wahlström, Annika

AU - Kovatcheva-Datchary, Petia

AU - Ståhlman, Marcus

AU - Khan, Muhammad-Tanweer

AU - Bäckhed, Gert Fredrik

AU - Marschall, Hanns-Ulrich

N1 - Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

PY - 2017/2

Y1 - 2017/2

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1194/jlr.m072819

DO - 10.1194/jlr.m072819

M3 - Journal article

C2 - 27956475

SN - 0022-2275

VL - 58

SP - 412

EP - 419

JO - Journal of Lipid Research

JF - Journal of Lipid Research

IS - 2

ER -