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6 alpha-hydroxylate...
6 alpha-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice
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- Makki, Kassem (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Brolin, Harald, 1992 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Petersen, N. (författare)
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visa fler...
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- Henricsson, Marcus, 1975 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Christensen, D. P. (författare)
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- Khan, Muhammad Tanweer (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Wahlström, Annika, 1975 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bergh, Per-Olof (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Tremaroli, Valentina, 1978 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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Schoonjans, K. (författare)
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- Marschall, Hanns-Ulrich, 1954 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Bäckhed, Fredrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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(creator_code:org_t)
- 2022-06-13
- 2023
- Engelska.
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 72:2, s. 314-324
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 6 alpha-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6 alpha-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 6 alpha-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 6 alpha-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- bile acid metabolism
- dietary fibre
- diabetes mellitus
- glucagen-like
- peptides
- gut microbiota
- muricholic acid
- promotes
- health
- glp-1
- consequences
- microflora
- resistance
- increases
- dysbiosis
- Gastroenterology & Hepatology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Makki, Kassem
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Brolin, Harald, ...
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Petersen, N.
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Henricsson, Marc ...
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Christensen, D. ...
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Khan, Muhammad T ...
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visa fler...
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Wahlström, Annik ...
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Bergh, Per-Olof
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Tremaroli, Valen ...
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Schoonjans, K.
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Marschall, Hanns ...
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Bäckhed, Fredrik ...
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