A growing body of evidence supports the significance of the gut microbiome with respect to behavioral disorders, as mediated by disruption to the gut-brain axis. Importantly, there is a lack of understanding regarding associations between gut microbiome dysbiosis and behavioral phenotypic outcome. Traumatic childhood events early-in-life can result in later-in-life behavioral consequences. Maternal separation (MS) is an example of such an event that is represented with a well-established preclinical (i.e., animals) experimental model for early life stress. In a recent study, researcher’s sought to investigate the precise role of MS in the induction of changes to the gut microbiomes of mice, and the potential behavior phenotypic consequences brought on by these changes.
C57 mice were subject to three unique experimental groups: germ-free (GF) mice, specific pathogen-free mice (SPF, i.e. mice with microbiome compositions), and germ-free mice that were eventually subject to recolonization. Mice were either left alone after birth or exposed to MS 3 days after birth. Behavior was examined after 8 weeks, and the germ-free group was sacrificed after 9-10 weeks and the SPF group after 16-20 weeks. The recolonization group was recolonized with microbiota at 12-13 weeks, followed by more behavioral tests and subsequent sacrificed.
Corticosterone - a major stress hormone - was significantly elevated in both GF and SPF mice that were subjected to MS. The researchers next wanted to define a relationship between the host microbiome and anxiety-like behaviors weeks after being separated from the mothers. It was fist observed that MS did indeed alter microbiota composition in SPF mice. Interestingly, MS-induced anxiety like behavior was observed in SPF mice, but not in GF mice, suggesting that the microbiome played a significant role in the development of these types of behaviors. The experimenters then recolonized the guts of a subgroup of GF mice. Indeed, behavior was altered in MS mice whose guts were colonized as compared to the MS mice that remained germ free. Other physiological indicators demonstrated significant interactions between MS and the presence of gut microbiota, as gut microbiota presence had a significant impact on noradrenaline and serotonin levels.
All told, the findings in this study suggest microbiome dysbiosis is a critical physiological driving force behind the behavioral phenotypes associated with early life stress events. It will next be important to begin thinking about translate these preclinical findings in a clinical setting, in hopes of exploring ways to help those in need.