6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice. / Makki, Kassem; Brolin, Harald; Petersen, Natalia; Henricsson, Marcus; Christensen, Dan Ploug; Khan, Muhammad Tanweer; Wahlström, Annika; Bergh, Per-Olof; Tremaroli, Valentina; Schoonjans, Kristina; Marschall, Hanns-Ulrich; Bäckhed, Fredrik.

In: Gut, Vol. 72, 2023, p. 314-324.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Makki, K, Brolin, H, Petersen, N, Henricsson, M, Christensen, DP, Khan, MT, Wahlström, A, Bergh, P-O, Tremaroli, V, Schoonjans, K, Marschall, H-U & Bäckhed, F 2023, '6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice', Gut, vol. 72, pp. 314-324. https://doi.org/10.1136/gutjnl-2021-326541

APA

Makki, K., Brolin, H., Petersen, N., Henricsson, M., Christensen, D. P., Khan, M. T., Wahlström, A., Bergh, P-O., Tremaroli, V., Schoonjans, K., Marschall, H-U., & Bäckhed, F. (2023). 6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice. Gut, 72, 314-324. https://doi.org/10.1136/gutjnl-2021-326541

Vancouver

Makki K, Brolin H, Petersen N, Henricsson M, Christensen DP, Khan MT et al. 6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice. Gut. 2023;72:314-324. https://doi.org/10.1136/gutjnl-2021-326541

Author

Makki, Kassem ; Brolin, Harald ; Petersen, Natalia ; Henricsson, Marcus ; Christensen, Dan Ploug ; Khan, Muhammad Tanweer ; Wahlström, Annika ; Bergh, Per-Olof ; Tremaroli, Valentina ; Schoonjans, Kristina ; Marschall, Hanns-Ulrich ; Bäckhed, Fredrik. / 6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice. In: Gut. 2023 ; Vol. 72. pp. 314-324.

Bibtex

@article{c4aad58272194a47b4e652b304581242,
title = "6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice",
abstract = "OBJECTIVE: Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising the fibres. Here, we investigated whether the soluble dietary fibre oligofructose improves host metabolism by modulating bacterial transformation of secondary bile acids in mice fed western-style diet.DESIGN: To assess the impact of dietary fibre supplementation on bile acid transformation by gut bacteria, we fed conventional wild-type and TGR5 knockout mice western-style diet enriched or not with cellulose or oligofructose. In addition, we used germ-free mice and in vitro cultures to evaluate the activity of bacteria to transform bile acids in the caecal content of mice fed with western-style diet enriched with oligofructose. Finally, we treated wild-type and TGR5 knockout mice orally with hyodeoxycholic acid to assess its antidiabetic effects.RESULTS: We show that oligofructose sustains the production of 6α-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6α-hydroxylated bile acids were microbiota dependent and specifically required functional TGR5 signalling to reduce body weight gain and improve glucose metabolism. Furthermore, we show that the 6α-hydroxylated bile acid hyodeoxycholic acid stimulates TGR5 signalling, in vitro and in vivo, and increases GLP-1R activity to improve host glucose metabolism.CONCLUSION: Modulation of the gut microbiota with oligofructose enriches bacteria involved in 6α-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.",
author = "Kassem Makki and Harald Brolin and Natalia Petersen and Marcus Henricsson and Christensen, {Dan Ploug} and Khan, {Muhammad Tanweer} and Annika Wahlstr{\"o}m and Per-Olof Bergh and Valentina Tremaroli and Kristina Schoonjans and Hanns-Ulrich Marschall and Fredrik B{\"a}ckhed",
note = "{\textcopyright} Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.",
year = "2023",
doi = "10.1136/gutjnl-2021-326541",
language = "English",
volume = "72",
pages = "314--324",
journal = "Gut",
issn = "0017-5749",
publisher = "B M J Group",

}

RIS

TY - JOUR

T1 - 6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice

AU - Makki, Kassem

AU - Brolin, Harald

AU - Petersen, Natalia

AU - Henricsson, Marcus

AU - Christensen, Dan Ploug

AU - Khan, Muhammad Tanweer

AU - Wahlström, Annika

AU - Bergh, Per-Olof

AU - Tremaroli, Valentina

AU - Schoonjans, Kristina

AU - Marschall, Hanns-Ulrich

AU - Bäckhed, Fredrik

N1 - © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

PY - 2023

Y1 - 2023

N2 - OBJECTIVE: Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising the fibres. Here, we investigated whether the soluble dietary fibre oligofructose improves host metabolism by modulating bacterial transformation of secondary bile acids in mice fed western-style diet.DESIGN: To assess the impact of dietary fibre supplementation on bile acid transformation by gut bacteria, we fed conventional wild-type and TGR5 knockout mice western-style diet enriched or not with cellulose or oligofructose. In addition, we used germ-free mice and in vitro cultures to evaluate the activity of bacteria to transform bile acids in the caecal content of mice fed with western-style diet enriched with oligofructose. Finally, we treated wild-type and TGR5 knockout mice orally with hyodeoxycholic acid to assess its antidiabetic effects.RESULTS: We show that oligofructose sustains the production of 6α-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6α-hydroxylated bile acids were microbiota dependent and specifically required functional TGR5 signalling to reduce body weight gain and improve glucose metabolism. Furthermore, we show that the 6α-hydroxylated bile acid hyodeoxycholic acid stimulates TGR5 signalling, in vitro and in vivo, and increases GLP-1R activity to improve host glucose metabolism.CONCLUSION: Modulation of the gut microbiota with oligofructose enriches bacteria involved in 6α-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.

AB - OBJECTIVE: Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising the fibres. Here, we investigated whether the soluble dietary fibre oligofructose improves host metabolism by modulating bacterial transformation of secondary bile acids in mice fed western-style diet.DESIGN: To assess the impact of dietary fibre supplementation on bile acid transformation by gut bacteria, we fed conventional wild-type and TGR5 knockout mice western-style diet enriched or not with cellulose or oligofructose. In addition, we used germ-free mice and in vitro cultures to evaluate the activity of bacteria to transform bile acids in the caecal content of mice fed with western-style diet enriched with oligofructose. Finally, we treated wild-type and TGR5 knockout mice orally with hyodeoxycholic acid to assess its antidiabetic effects.RESULTS: We show that oligofructose sustains the production of 6α-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6α-hydroxylated bile acids were microbiota dependent and specifically required functional TGR5 signalling to reduce body weight gain and improve glucose metabolism. Furthermore, we show that the 6α-hydroxylated bile acid hyodeoxycholic acid stimulates TGR5 signalling, in vitro and in vivo, and increases GLP-1R activity to improve host glucose metabolism.CONCLUSION: Modulation of the gut microbiota with oligofructose enriches bacteria involved in 6α-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.

U2 - 10.1136/gutjnl-2021-326541

DO - 10.1136/gutjnl-2021-326541

M3 - Journal article

C2 - 35697422

VL - 72

SP - 314

EP - 324

JO - Gut

JF - Gut

SN - 0017-5749

ER -

ID: 311338104