Bacterial infection causes stress-induced memory dysfunction in mice

Gut. 2011 Mar;60(3):307-17. doi: 10.1136/gut.2009.202515. Epub 2010 Oct 21.


Background: The brain-gut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established.

Objective: To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation.

Methods: Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated.

Results: No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota.

Conclusions: The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / microbiology
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / metabolism
  • Citrobacter rodentium*
  • Colon / pathology
  • Corticosterone / blood
  • Cytokines / biosynthesis
  • Enterobacteriaceae Infections / metabolism
  • Enterobacteriaceae Infections / psychology*
  • Feces / microbiology
  • Female
  • Germ-Free Life
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Hyperplasia / microbiology
  • Hyperplasia / prevention & control
  • Inflammation Mediators / metabolism
  • Memory Disorders / etiology*
  • Memory Disorders / microbiology
  • Memory Disorders / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Probiotics / therapeutic use
  • Proto-Oncogene Proteins c-fos / metabolism
  • Stress, Psychological / blood
  • Stress, Psychological / psychology*


  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Inflammation Mediators
  • Proto-Oncogene Proteins c-fos
  • Corticosterone