Nature Communications (Nov 2023)

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,
  • Shaoping Nie

DOI
https://doi.org/10.1038/s41467-023-43622-3
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 16

Abstract

Read online

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.