Multi-hit early life adversity affects gut microbiota, brain and behavior in a sex-dependent manner.
Animals
Animals, Newborn
Anxiety
/ metabolism
Behavior, Animal
/ physiology
Brain
/ metabolism
Dysbiosis
/ metabolism
Female
Gastrointestinal Microbiome
/ physiology
Male
Maternal Deprivation
Mice
Mice, Inbred C3H
Microbiota
Prefrontal Cortex
/ metabolism
Sex Factors
Social Behavior
Stress, Psychological
/ metabolism
Early-life stress
Emotional behavior
Gut-brain axis
HPA axis
Intestinal permeability
Lipopolysaccharides
Medial prefrontal cortex
Ultrasonic vocalizations
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
09
09
2018
revised:
22
02
2019
accepted:
09
03
2019
pubmed:
16
3
2019
medline:
2
6
2020
entrez:
16
3
2019
Statut:
ppublish
Résumé
The accumulation of adverse events in utero and during childhood differentially increases the vulnerability to psychiatric diseases in men and women. Gut microbiota is highly sensitive to the early environment and has been recently hypothesized to affect brain development. However, the impact of early-life adversity on gut microbiota, notably with regards to sex differences, remains to be explored. 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 (lipopolysaccharide injection on embryonic day 17, 120 µg/kg, i.p.), 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 in the elevated plus maze and increased compulsive behavior in the marble burying test. 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 psychiatric research.
Identifiants
pubmed: 30872090
pii: S0889-1591(18)30570-1
doi: 10.1016/j.bbi.2019.03.006
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
179-192Informations de copyright
Copyright © 2019. Published by Elsevier Inc.