Influence of age, sex, and location on the diversity of the murine gut microbiome and/or expression of pro-inflammatory cytokines

Abstract The microbiome and immune system have a unique interplay, which influences homeostasis within the organism. Both the microbiome and immune system play important roles in health and in diseases of the aged. Various groups have demonstrated divergent changes in gut microbiota during aging, but these studies have largely ignored the compounding factor of biological sex in this aging, and little is known about the effect of institutional environment on the composition of gut microbiota in normal healthy mice. To better understand the roles of sex, aging, and environment in influencing the gut microbiome, we obtained normal healthy BALB/cByJ mice from a single source and aged male and female mice in two different geographical locations. A 16s rRNA microbiome analysis indicated that both age and sex play a role in microbiome composition; additionally, location plays a role in the diversity present as well. Interestingly, these microbiome changes occurred with changes in serum expression of several different pro-inflammatory cytokines including IL-10 and IL-6, which were also both differentially regulated in context to sex and aging. B-1a cells are known to produce mucosal IgA as well as IL-10 and IL-6, which play roles in regulating the microbiome. Furthermore, we found both IL-10 and IL-6 play a role in the constitutive expression of pSTAT-3 in B-1a cells. Together these results demonstrate sex and age shape the gut microbiome as well as systemic cytokine expression, which can influence, and be influenced by B-1a cells. In addition, location of housing can also influence the microbiome despite common animal sourcing. These results emphasize the importance of sex, age, and housing location in the mechanism of development of the gut microbiome. Supported by NIAID of the NIH (R01AI154539)