Elsevier

Biological Psychiatry

Volume 65, Issue 3, 1 February 2009, Pages 263-267
Biological Psychiatry

Research Report
Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses

https://doi.org/10.1016/j.biopsych.2008.06.026Get rights and content

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.

Section snippets

Animals

Two cohorts of 2x22 Sprague Dawley rat pups were used in these studies. The pups were housed with their mothers in plastic cages (15 × 22 × 9 cm). The animal room remained temperature-controlled (20 ± 1°C) and on 12-hour light/dark cycle (lights on at 7:00 am).

There were two groups: maternally separated (MS) (n = 11) and non-separated (NS) (n = 11). This study was powered to detect differences at the .05 level. The ethical committee of University College Cork approved the experimental procedure.

Statistical Analysis

All data were normally distributed according to Gaussian distribution analysis. All data are expressed as mean ± SEM. Student t tests were conducted in all in vivo studies except for the cumulative number of visceral pain-related behaviors, where a random coefficient power analysis was used. A two-way analysis of variance (ANOVA) was used to analyze the CRD and the open field data globally. Dendrograms of DGGE banding profiles were constructed to visualize any clustering patterns evident and to

Novel Stress/Open Field

The average number of fecal pellets produced by the MS group was significantly greater (3.1 ± .5 vs. 1.7 ± .3) compared with the NS group [t(22) = 2.45, p < .05].

CRD

In the MS group there was a decrease in the threshold (p < .05) (Figure 1A), compared with control animals. Moreover, there was also an increase in the number of cumulative pain behaviors (p < .05) (Figure 1B). A two-way ANOVA revealed an interaction between pressure and maternal separation [p < .001, F(7,160) = 4.18]. There was also

Discussion

The MS animals displayed diverse phenotypic changes, which is indicative of comorbid anxiety/stress and functional bowel disorders. These occur at a multifunctional level with behavioral alterations suggestive of increased anxiety and visceral hypersensitivity, physiological alterations including elevated HPA-axis function, and increased systemic immune responses; finally, perturbations in gut microbiota were also observed. Together, these data indicate that early life stress induces persistent

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