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Long term but not short term exposure to obesity related microbiota promotes host insulin resistance

Kevin P Foley1, Soumaya Zlitni2, Emmanuel Denou1

  • 1Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute McMaster University, Hamilton, L8N 3Z5, ON, Canada.

Nature Communications
|November 10, 2018
PubMed

Insights

Changes in gut microbiota precede glucose intolerance in mice on high-fat diets (HFDs). Prolonged exposure to obesity-related microbes contributes to chronic insulin resistance and dysglycemia.

Area of Science:

  • Microbiology
  • Metabolism
  • Endocrinology

Background:

  • Obesogenic diets rapidly alter intestinal microbiota and insulin sensitivity.
  • Diet-induced changes in fecal microbiota composition can precede alterations in glucose tolerance.

Purpose of the Study:

  • To investigate the temporal relationship between gut microbiota changes and the development of insulin resistance and dysglycemia.
  • To determine the role of host exposure time to obesity-related microbes in metabolic dysfunction.

Main Methods:

  • Mice were fed obesogenic, high-fat diets (HFDs).
  • Changes in fecal microbiota composition, glycemia, and glucose tolerance were monitored.
  • Germ-free mice were exposed to microbiota from HFD-fed mice for varying durations.

Main Results:

  • Microbiota alterations preceded glucose tolerance changes in mice on HFDs.
  • Antibiotics improved glycemic control in mice with protracted obesity.
  • Transmissible dysglycemia and glucose intolerance required over 45 days of exposure to obesity-related microbes.
  • Microbial factors contributed to insulin resistance independently of adiposity after sufficient host exposure time.

Conclusions:

  • The intestinal microbiota contributes to chronic insulin resistance and dysglycemia during prolonged obesity.
  • Sufficient host exposure time to specific microbial communities is crucial for the development of diet-induced metabolic dysfunction.

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