Parabacteroides Distasonis Ameliorates Insulin Resistance Via Activation of Intestinal GPR109a

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Nov 25

PMID 38007572

Authors

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

Affiliations

Soon will be listed here.

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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