Abstract

Sex outcome and maternal investment in progeny are important predictors of reproductive success. While environmental factors appear to influence these processes, there is little evidence to date of a direct role for gut commensals. Here we show that the reproductive outcomes (sex and survival) of mouse litters depend on signals conveyed through the microbiome. We discover that transient treatment of mouse mothers with specific microorganisms increases the absolute survival of offspring and skews offspring sex ratios via an endocrine-dependent mechanism requiring the neurophysiological hormone oxytocin. The implication of maternal oxytocin levels suggests that commensal microbes may have a broad role in modulating host endocrine and neurological pathways.

Highlights

  • Factors governing important predictors of reproductive success, such as maternal investment in progeny, remain poorly understood [1,2,3,4]

  • During a recent study we observed that female mice consuming Lactobacillus reuteri (LR) showed more frequent grooming activity, an aspect of maternal behavior regulated by neurohypophyseal hormone oxytocin [19,20,21]

  • Our results suggest that the distribution of sex ratios in mice differs depending on maternal gut microbes that influence these outcomes through a neurophysiological and, in particular, oxytocin-dependent mechanism

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Summary

Introduction

Factors governing important predictors of reproductive success, such as maternal investment in progeny, remain poorly understood [1,2,3,4]. It is known that consumption of a Westernized diet can alter the microbiota in mice [9,10,11,12] commensurate with infanticide, leading us to postulate a microbe-dependent mechanism of action in maternal investment To test this hypothesis, we surveyed C57BL/6 mice to determine whether there were changes in the survival of offspring and sex ratio associated with targeted consumption of a specific microorganism. Recent evidence suggests a role for oxytocin in autism spectrum disorder [42] and post-partum depression, as well as pair bonding, anxiety, and maternal care [43,44,45,46,47] Because these and other social and reproductive disorders implicate oxytocin, there is great interest in assessing whether an underlying microbial determinant may be modifying the central nervous system vis-à-vis direct or indirect influence on the activity of oxytocin in the body. The centrality of oxytocin in these outcomes suggests potential associations with autism and post-partum depression [42,43], offering promise for gut microbe therapy in these and related disorders

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