Involvement of the microbiota-gut-brain axis in chronic restraint stress: disturbances of the kynurenine metabolic pathway in both the gut and brain

Feb 4, 2021Gut microbes

Chronic stress may disrupt a key chemical pathway in the gut and brain linked to the microbiome-gut-brain connection

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Abstract

Chronic restraint stress (CRS) in mice resulted in significant changes in tryptophan metabolism and behavior linked to depression and anxiety.

  • Mice subjected to CRS exhibited behaviors indicative of depression and anxiety.
  • Activation of the metabolic pathway was strongly observed in the brain of CRS mice.
  • Increased toxic signaling from kynurenine was particularly pronounced in the colon of CRS mice.
  • Indoleamine 2,3-dioxygenase (IDO) levels were significantly higher in both the brain and gut of CRS mice, indicating altered tryptophan metabolism.
  • Administration of an IDO inhibitor partially alleviated depression- and anxiety-like behaviors in CRS mice.
  • CRS increased intestinal permeability, allowing toxic metabolites to enter the bloodstream, which correlated with altered gut microbiome composition.

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Key numbers

3 of 10
Increase in levels
levels in the brain and gut compared to control mice.
50%
Decrease in sucrose consumption
Sucrose consumption ratio in CRS mice vs. control mice.

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