The Effect of Microbial Composition on Acute Immune Responsivity in Pubertal Male and Female CD1 Mice

Abstract

The gut microbiome plays a quintessential role in the development and maintenance of the neuro-immune system throughout lifespan. Changes in microbial composition during critical periods of development—such as puberty—are associated with long-term disruptions in brain function and neuro-immune responsivity. However, the mechanisms underlying the effect of microbial dysbiosis on the pubertal neuro-immune response has yet to be elucidated. Therefore, the current thesis was designed to investigate the effect of changes in gut microbial composition (through antibiotic and probiotic exposure) in pubertal male and female mice on acute lipopolysaccharide (LPS)-induced immune response. Male and female CD1 mice were treated with one week of antibiotic treatment (mixed antibiotics or water) and probiotic treatment (lacidofil, probio’stick, or placebo) at five weeks of age. At six weeks of age (pubertal stress-sensitive period), the mice received a single injection of LPS or saline. Sickness behaviours were assessed and mice were euthanized at eight hours’ post-injection. Brain, blood, and intestinal measures were collected. The results indicated that the antibiotic treatment reduced sickness behaviours, increased LPS-induced plasma cytokine concentrations, and LPS-induced hippocampal pro-inflammatory markers in a sexually dimorphic manner. Probiotics reduced LPS-induced plasma cytokine concentrations and hippocampal pro-inflammatory markers in a sexually dimorphic manner. Lacidofil supplementation mitigated antibiotic-induced plasma cytokine concentrations and sickness behaviours. These findings suggest that the microbiome is an important modulator of the pro-inflammatory immune response during puberty. These results also have implications for the neuro-immune mechanisms with which gut dysfunctions influence brain function and behaviours.