1. Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids
- Author
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Nan Zhou, Mingfang Liao, Shuang-Jiang Liu, Li Bao, Wenzhao Wang, Yu-Jing Wang, Hongwei Liu, Ke Ma, Chang Liu, Zhongyong Zheng, Kai Wang, and Jun Wang
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Lithocholic acid ,medicine.drug_class ,Succinic Acid ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Bile Acids and Salts ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Bacterial Proteins ,Internal medicine ,Hyperlipidemia ,medicine ,Animals ,Humans ,Obesity ,Bile acid ,Chemistry ,Bacteroidetes ,Metabolism ,medicine.disease ,Ursodeoxycholic acid ,Gastrointestinal Microbiome ,030104 developmental biology ,Endocrinology ,Gluconeogenesis ,Parabacteroides distasonis ,Steatosis ,030217 neurology & neurosurgery ,medicine.drug - Abstract
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.
- Published
- 2018