Social instability stress (SS; daily 1 h isolation and change of cage partner from postnatal day (P) 30–45) in adolescence produces elevations in corticosterone during the procedure in male and female rats, but no lasting changes in hypothalamic-pituitary-adrenal (HPA) responses to psychological stressors, although deficits in social and cognitive function are evident in adulthood. Here we investigated the effects of SS in corticosterone response to an immune challenge (lipopolysaccharide, LPS, 0.1 mg/kg), on gene expression in the hippocampus, and on gut microbiota, when tested soon- (P46) or long- (P70) after SS. The temporal pattern of corticosterone release after LPS differed between SS and control rats irrespective of the time since SS exposure in females, whereas in males, SS did not alter corticosterone release after LPS. Expression of genes in the hippocampus relevant to immune and HPA function differed between saline-treated SS and control rats depending on sex and time tested, but with lasting consequences of SS in both sexes. LPS-treatment altered hippocampal gene expression, with bigger effects of LPS evident in control than in SS female rats, and the opposite in male rats. Further, effects sometimes depended on the age at time of LPS treatment. SS and control rats differed in both fecal and colon microbiome composition in all but P46 males, and stress history, sex, and age influenced the effects of an immune challenge on the gut microbiome. In sum, adolescent stress history has consequences for immune function into adulthood that may involve effects on the gut microbiome.

青春期的社交不稳定压力（SS；每天从出生后第30-45天分离1 h并改变笼伴侣）在雄性和雌性大鼠的过程中会导致皮质酮升高，但下丘脑-垂体-肾上腺没有持久的变化（HPA）对心理压力源的反应，尽管成年后社交和认知功能均明显不足。在这里，我们研究了SS在对皮质类固醇激素的免疫应答（脂多糖，LPS，0.1 mg / kg），海马和肠道菌群中的基因表达的影响（当进行短期（-P46）或长期（P70）测试时）在SS之后。SS和对照组大鼠在LPS后皮质酮释放的时间模式各不相同，而与雌性自SS暴露以来的时间无关，而在雄性大鼠中，SS并没有改变LPS后皮质酮的释放。生理盐水处理过的SS和对照组大鼠海马中与免疫和HPA功能相关的基因表达有所不同，具体取决于性别和所测试的时间，但在男女中都有SS的持久后果。LPS处理改变了海马基因的表达，与对照组相比，LPS在对照组中的影响明显大于雌性大鼠，而雄性大鼠则相反。此外，效果有时取决于LPS治疗时的年龄。除P46雄性外，SS和对照组大鼠的粪便和结肠微生物组组成均不同，应激史，性别和年龄影响了免疫挑战对肠道微生物组的影响。总之，青春期应激史会对成年后的免疫功能产生影响，可能影响肠道微生物组。