Fetal programming of anxiety-related behavior and growth rate by the maternal microbiome

Anxiety disorders are becoming increasingly prevalent in the general population. The gut microbiome (GM) plays a role in central nervous system function, and differences in the taxonomic composition and richness of the GM have been associated with anxiety-related behavior. Recent studies show that mice with GM of low richness display higher levels of anxiety-related behavior and have an accelerated growth rate compared to mice with a high richness GM. Although the GM is known to influence these phenotypes, the influence of the maternal GM on the development of anxiety-related behavior and growth in offspring is unclear. This study sought to determine the relative influence of the maternal GM during pregnancy and the offspring GM during early life in the development of anxiety-related behavior and growth rate. Two colonies of CD1 mice harboring either a high richness GM (GM4) or low richness GM (GM1) were bred, and pups either stayed with their birth dam, or were cross-fostered to a surrogate dam of the opposite GM at less than 24 hours of age. Beginning at 35 days of age, mice (n =24 to 40/sex/group) underwent multiple behavior tests used to assess anxiety-related behavior, including open-field exploration (OFE), light/dark transition (LDT), and elevated plus maze (EPM). LDT and EPM tests showed that GM4 pups cross-fostered to a GM1 surrogate dam displayed less anxiety-related behavior than GM1 mice cross-fostered to a GM4 surrogate dam (p < 0.05), recapitulating the anxiety-related behavior phenotype of their birth dams instead of surrogate dams. Similarly, while GM1 mice showed faster growth than GM4 mice when mice were reared on their birth dams, GM4 pups cross-fostered to GM1 surrogate dams gained more weight than GM1 mice cross-fostered to GM4 surrogate dams (p < 0.05). Single cell gene expression analysis found increased neuronal expression of multiple glutamate receptors in hippocampus of mice with GM1.These results suggest that the maternal GM influences offspring development in utero, resulting in effects lasting into adulthood.