Bacterial infection causes stress-induced memory dysfunction in mice.
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.
Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada. philip.sherman@sickkids.ca
Mélanie G
MG
Gareau
Eytan
E
Wine
David M
DM
Rodrigues
Joon Ho
JH
Cho
Mark T
MT
Whary
Dana J
DJ
Philpott
Glenda
G
Macqueen
Philip M
PM
Sherman
D000818:Animals; D001007:Anxiety / Q000382:microbiology; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D044082:Citrobacter rodentium; D003106:Colon / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D004756:Enterobacteriaceae Infections / Q000378:metabolism / Q000523:psychology*; D005243:Feces / Q000382:microbiology; D005260:Female; D005856:Germ-Free Life; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006965:Hyperplasia / Q000382:microbiology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D008569:Memory Disorders / Q000209:etiology* / Q000382:microbiology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood / Q000523:psychology*
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D018836:Inflammation Mediators; D016760:Proto-Oncogene Proteins c-fos; D003345:Corticosterone