The Effects of Probiotic Treatment During Puberty on LPS-Induced Immune Response in Male and Female Mice

Abstract

Puberty is a critical developmental period that is particularly vulnerable to stress and inflammation. In mice, exposure to an immune challenge (lipopolysaccharide; LPS) during puberty causes enduring effects on depression- and anxiety-like behaviour into adulthood. While the mechanisms underlying these effects remain unknown, the gut microbiome could play a role in mediating the immune system and can alter brain functioning. Thus, we investigated if colonizing the gut with beneficial microbes via probiotics could mediate the inflammatory response to pubertal LPS treatment, in 80 male and female CD1 mice. Sickness behaviour and pro-inflammatory cytokine mRNA expression via RT-qPCR were examined. LPS treatment increased sickness and inflammation in all mice. However, LPS-treated males showed more sickness behaviour, but less central cytokine mRNA expression compared to females and their control saline-treated counterparts. These effects were eliminated when the mice were treated with probiotics. In females, probiotic treatment reduced sickness behaviour, in a time-specific manner, and reduced cytokine mRNA expression in a region-specific manner following LPS treatment. Our results show that probiotics mitigate the LPS-induced immune response differently between males and females. These findings suggest that probiotics have a protective effect during puberty and may prevent the onset of mental health conditions like depression and anxiety.