Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a

Yonggan Sun, Qixing Nie, Shanshan Zhang, Huijun He, Sheng Zuo, Chunhua Chen, Jingrui Yang, Haihong Chen, Jielun Hu, Song Li, Jiaobo Cheng, Baojie Zhang, Zhitian Zheng, Shijie Pan, Ping Huang, Lu Lian and Shaoping Nie ()
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Yonggan Sun: Nanchang University
Qixing Nie: Nanchang University
Shanshan Zhang: Nanchang University
Huijun He: Nanchang University
Sheng Zuo: Nanchang University
Chunhua Chen: Nanchang University
Jingrui Yang: Nanchang University
Haihong Chen: Nanchang University
Jielun Hu: Nanchang University
Song Li: Nanchang University
Jiaobo Cheng: Nanchang University
Baojie Zhang: Nanchang University
Zhitian Zheng: Nanchang University
Shijie Pan: Nanchang University
Ping Huang: the First Affiliated Hospital of Nanchang University
Lu Lian: the First Affiliated Hospital of Nanchang University
Shaoping Nie: Nanchang University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.

Date: 2023
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DOI: 10.1038/s41467-023-43622-3

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