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Updated: Jul 10, 2025

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a
Yonggan Sun1,2,3, Qixing Nie1,2,3, Shanshan Zhang1,2,3
1State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China.
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.
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