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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.
Here, the authors show that the gut commensal Parabacteroides distasonis alleviates insulin resistance via nicotinic acid-intestinal GPR109a axis activation, a process promoted by Dendrobium officinale polysaccharide.
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Details
1 Nanchang University, State Key Laboratory of Food Science and Resources, Nanchang, China (GRID:grid.260463.5) (ISNI:0000 0001 2182 8825); Nanchang University, China-Canada Joint Lab of Food Science and Technology, Nanchang, China (GRID:grid.260463.5) (ISNI:0000 0001 2182 8825); Nanchang University, Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang, China (GRID:grid.260463.5) (ISNI:0000 0001 2182 8825)
2 Nanchang University, State Key Laboratory of Food Science and Resources, Nanchang, China (GRID:grid.260463.5) (ISNI:0000 0001 2182 8825)
3 the First Affiliated Hospital of Nanchang University, Department of Nutrition, Nanchang, China (GRID:grid.412604.5) (ISNI:0000 0004 1758 4073)