Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss

Sébastien Lucas, Yasunori Omata, Jörg Hofmann, Martin Böttcher, Aida Iljazovic, Kerstin Sarter, Olivia Albrecht, Oscar Schulz, Brenda Krishnacoumar, Gerhard Krönke, Martin Herrmann, Dimitrios Mougiakakos, Till Strowig, Georg Schett and Mario M. Zaiss ()
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Sébastien Lucas: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Yasunori Omata: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Jörg Hofmann: Friedrich-Alexander University Erlangen-Nürnberg (FAU)
Martin Böttcher: University Hospital Erlangen
Aida Iljazovic: Helmholtz Centre for Infection Research
Kerstin Sarter: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Olivia Albrecht: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Oscar Schulz: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Brenda Krishnacoumar: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Gerhard Krönke: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Martin Herrmann: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Dimitrios Mougiakakos: University Hospital Erlangen
Till Strowig: Helmholtz Centre for Infection Research
Georg Schett: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Mario M. Zaiss: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Microbial metabolites are known to modulate immune responses of the host. The main metabolites derived from microbial fermentation of dietary fibers in the intestine, short-chain fatty acids (SCFA), affect local and systemic immune functions. Here we show that SCFA are regulators of osteoclast metabolism and bone mass in vivo. Treatment of mice with SCFA as well as feeding with a high-fiber diet significantly increases bone mass and prevents postmenopausal and inflammation-induced bone loss. The protective effects of SCFA on bone mass are associated with inhibition of osteoclast differentiation and bone resorption in vitro and in vivo, while bone formation is not affected. Mechanistically, propionate (C3) and butyrate (C4) induce metabolic reprogramming of osteoclasts resulting in enhanced glycolysis at the expense of oxidative phosphorylation, thereby downregulating essential osteoclast genes such as TRAF6 and NFATc1. In summary, these data identify SCFA as potent regulators of osteoclast metabolism and bone homeostasis.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02490-4

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DOI: 10.1038/s41467-017-02490-4

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