Sex-specific impact of neonatal maternal separation on fecal microbiota signatures in young adult mice

Stressful events during the neonatal period result in alterations of intestinal homeostasis and predispose to brain-gut axis related disorders in adulthood. Maternal separation (MS) induces visceral hypersensitivity of 50-days old female and male C3H/HeN mice but selectively increases intestinal permeability of male. Considering that gut microbial colonization overlaps with MS, we addressed in this study subsequent consequences on their fecal microbiota. Methodology. Relative abundances of 21 microbial communities were compared using the GUt-Low-Density-Array approach and analysed using multivariate approaches. Results. Microbial profiles of adult male and female clustered separately regardless of MS in early life. Alteration in response to MS was more pronounced in male than female. Among the  microbial determinants associated with MS, a diminution of Roseburia spp. was observed in both sexes, whereas diminution of Bifidobacterium spp. and increase of Clostridium butyricum were male-specific. Divergent responses according to sex were observed regarding relative abundances of Methanobrevibacter smithii, Enterobacteriaceae and Eubacterium hallii. Conclusion. Sexual dimorphism highlighted in this study reflects previously observed host functional dimorphisms. Identification of stages at which each event occurs early in life may help to understand whether theses microbial alterations are a cause or a consequence of adverse outcomes in adulthood.