Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses.
BACKGROUND
Adverse early life events are associated with a maladaptive stress response system and might increase the vulnerability to disease in later life. Several disorders have been associated with early life stress, ranging from depression to irritable bowel syndrome. This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable.


METHODS
The purpose of this study was to assess the effect of early life stress on the brain-gut axis. Male rat pups were stressed by separating them from their mothers for 3 hours daily between postnatal days 2-12. The control group was left undisturbed with their mothers. Behavior, immune response, stress sensitivity, visceral sensation, and fecal microbiota were analyzed.


RESULTS
The early life stress increased the number of fecal boli in response to a novel stress. Plasma corticosterone was increased in the maternally separated animals. An increase in the systemic immune response was noted in the stressed animals after an in vitro lipopolysaccharide challenge. Increased visceral sensation was seen in the stressed group. There was an alteration of the fecal microbiota when compared with the control group.


CONCLUSIONS
These results show that this form of early life stress results in an altered brain-gut axis and is therefore an important model for investigating potential mechanistic insights into stress-related disorders including depression and IBS.
O'Mahony
Siobhain M
SM
Alimentary Pharmabiotic Centre, Cork, Ireland. somahony@ucc.ie
Marchesi
Julian R
JR
Scully
Paul
P
Codling
Caroline
C
Ceolho
Anne-Marie
AM
Quigley
Eamonn M M
EM
Cryan
John F
JF
Dinan
Timothy G
TG
D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004269:DNA, Bacterial / Q000032:analysis / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D005243:Feces / Q000737:chemistry; D005434:Flow Cytometry; D006728:Hormones / Q000097:blood; D043183:Irritable Bowel Syndrome / Q000276:immunology* / Q000382:microbiology* / Q000523:psychology; D008070:Lipopolysaccharides / Q000494:pharmacology; D001523:Mental Disorders / Q000276:immunology* / Q000382:microbiology* / Q000523:psychology; D009691:Nucleic Acid Denaturation; D010812:Physical Stimulation; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000276:immunology* / Q000382:microbiology* / Q000523:psychology
D016207:Cytokines; D004269:DNA, Bacterial; D006728:Hormones; D008070:Lipopolysaccharides; D012336:RNA, Ribosomal, 16S; D003345:Corticosterone