Modulating Effects of Environmental Enrichment on Stress-induced changes in the Gut Microbiome

Environmental enrichment (EE) involves adding non-standard stimuli, such as running wheels, mazes, and cage mates, to standard animal living conditions to facilitate physical activity, cognitive stimulation, and socialization. Interestingly, exposure to EE can modulate stress and immune responses. However, it is unclear whether housing environments can modulate the effects of stress on the gut microbiome. This study aimed to explore the effects of three different housing conditions - deprived (DH), social (SH), and enriched (EE) - on the central and peripheral immune responses, the HPA axis, and the gut microbiome in 180 male and female mice. Mice were housed in either the DH, SH, or EE condition for 3 weeks. At 6 weeks of age, during the pubertal stress-sensitive period, mice were treated with either saline or lipopolysaccharide (LPS), a bacterial endotoxin. Contrary to expectations, EE and SH mice showed higher plasma concentrations of TNFalpha, IL6, and IL12 cytokines than DH mice following LPS treatment, with male mice exhibiting significantly higher levels of these cytokines than their female counterparts. The gut microbiome analysis revealed sex-specific beta diversity patterns post-LPS treatment and will help enhance our understanding of how housing conditions influence acute immune and stress responses and also modulates their effects on the gut microbiome during puberty.