Crosstalk between Bile Acids and Gut Microbiota and Its Impact on Farnesoid X Receptor Signalling

TY - JOUR

T1 - Crosstalk between Bile Acids and Gut Microbiota and Its Impact on Farnesoid X Receptor Signalling

AU - Wahlström, Annika

AU - Kovatcheva-Datchary, Petia

AU - Ståhlman, Marcus

AU - Bäckhed, Fredrik

AU - Marschall, Hanns Ulrich

PY - 2017/3

Y1 - 2017/3

N2 - Background: 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. Conclusion: It is of special importance to elucidate how a human gut microbiota influences bile acid composition and FXR signalling in colonised mice.

AB - Background: 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. Conclusion: It is of special importance to elucidate how a human gut microbiota influences bile acid composition and FXR signalling in colonised mice.

KW - FXR agonism

KW - FXR antagonism

KW - Humanized mouse models

U2 - 10.1159/000450982

DO - 10.1159/000450982

M3 - Journal article

C2 - 28249261

AN - SCOPUS:85014694166

SN - 0257-2753

VL - 35

SP - 246

EP - 250

JO - Digestive Diseases

JF - Digestive Diseases

IS - 3

ER -