Cell Reports
Volume 26, Issue 1, 2 January 2019, Pages 222-235.e5
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Article
Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids

https://doi.org/10.1016/j.celrep.2018.12.028Get rights and content
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Highlights

  • Parabacteroides distasonis alleviates obesity and obesity-related dysfunctions in mice.

  • P. distasonis generates succinate and secondary bile acids in the gut.

  • P. distasonis activates intestinal gluconeogenesis (IGN) and FXR pathways in the gut.

  • Succinate is a ligand of fructose-1,6-bisphosphatase, the rate-limiting enzyme in IGN.

Summary

We demonstrated the metabolic benefits of Parabacteroides distasonis (PD) on decreasing weight gain, hyperglycemia, and hepatic steatosis in ob/ob and high-fat diet (HFD)-fed mice. Treatment with live P. distasonis (LPD) dramatically altered the bile acid profile with elevated lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) and increased the level of succinate in the gut. In vitro cultivation of PD demonstrated its capacity to transform bile acids and production of succinate. Succinate supplementation in the diet decreased hyperglycemia in ob/ob mice via the activation of intestinal gluconeogenesis (IGN). Gavage with a mixture of LCA and UDCA reduced hyperlipidemia by activating the FXR pathway and repairing gut barrier integrity. Co-treatment with succinate and LCA/UDCA mirrored the benefits of LPD. The binding target of succinate was identified as fructose-1,6-bisphosphatase, the rate-limiting enzyme in IGN. The succinate and secondary bile acids produced by P. distasonis played key roles in the modulation of host metabolism.

Keywords

Parabacteroides distasonis
bile acids
succinate
metabolic disorders
FBPase

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These authors contributed equally