Multi-hit early life adversity affects gut microbiota, brain and behavior in a sex-dependent manner.

We examined the effects of multifactorial early-life adversity on behavior and microbiota composition in C3H/HeN mice of both sexes exposed to a combination of maternal immune activation, maternal separation (3hr per day from postnatal day (PND)2 to PND14) and maternal unpredictable chronic mild stress. At adulthood, offspring exposed to multi-hit early adversity showed sex-specific behavioral phenotypes with males exhibiting deficits in social behavior and females showing increased anxiety and compulsive behavior in the elevated plus maze and marble burying tests. Early adversity also differentially regulated gene expression in the medial prefrontal cortex (mPFC) according to sex. Interestingly, several genes such as Arc, Btg2, Fosb, Egr4 or Klf2 were oppositely regulated by early adversity in males versus females. Finally, 16S-based microbiota profiling revealed sex-dependent gut dysbiosis. In males, abundance of taxa belonging to Lachnospiraceae and Porphyromonadaceae families or other unclassified Firmicutes, but also Bacteroides, Lactobacillus and Alloprevotella genera was regulated by early adversity. In females, the effects of early adversity were limited and mainly restricted to Lactobacillus and Mucispirillum genera. Our work reveals marked sex differences in a multifactorial model of early-life adversity, both on emotional behaviors and gut microbiota, suggesting that sex should systematically be considered in preclinical studies both in neurogastroenterology and ps...

Source: Brain, Behavior, and Immunity - March 10, 2019 Category: Neurology Authors: Rincel M, Aubert P, Chevalier J, Grohard PA, Basso L, de Oliveira CM, Helbling JC, Lévy É, Chevalier G, Leboyer M, Eberl G, Layé S, Capuron L, Vergnolle N, Neunlist M, Boudin H, Lepage P, Darnaudéry M Tags: Brain Behav Immun Source Type: research