Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period

Gilliard Lach,Timothy G Dinan,Ana Paula Ventura-Silva,Christine Fülling,John F Cryan,Aoife N O’ Donovan,Catherine Stanton,Thomaz F S Bastiaanssen,Fiona Fouhy

doi:10.1038/s41398-020-01073-0

Abstract

The gut microbiota is an essential regulator of many aspects of host physiology. Disruption of gut microbial communities affects gut-brain communication which ultimately can manifest as changes in brain function and behaviour. Transient changes in gut microbial composition can be induced by various intrinsic and extrinsic factors, however, it is possible that enduring shifts in the microbiota composition can be achieved by perturbation at a timepoint when the gut microbiota has not fully matured or is generally unstable, such as during early life or ageing. In this study, we investigated the effects of 3-week microbiota depletion with antibiotic treatment during the adolescent period and in adulthood. Following a washout period to restore the gut microbiota, behavioural and molecular hallmarks of gut-brain communication were investigated. Our data revealed that transient microbiota depletion had long-lasting effects on microbiota composition and increased anxiety-like behaviour in mice exposed to antibiotic treatment during adolescence but not in adulthood. Similarly, gene expression in the amygdala was more severely affected in mice treated during adolescence. Taken together these data highlight the vulnerability of the gut microbiota during the critical adolescent period and the long-lasting impact manipulations of the microbiota can have on gene expression and behaviour in adulthood.

Highlights

The adolescent period is a key developmental period which marks the transition from childhood to adulthood
Two-tailed Student’s t-test or Welch’s t-test were used for comparison between Control mice received autoclaved water (CTRL) and ABX for the elevated plus maze (EPM), Novel object recognition task (NORT), context and extinction recall in Fear conditioning (FC), and gene
As social behaviour and cognition have been shown to be impacted by alterations in gut microbiota composition, we investigated the effects of ABX treatment on measures in 3CSIT and NORT

Summary

Introduction

The adolescent period is a key developmental period which marks the transition from childhood to adulthood It is during this last developmental stage before adulthood that the brain is highly responsive to certain environmental cues that will shape neuronal architecture and promote maturation of social behaviours, emotional and cognitive capabilities and is a vulnerable period for the onset of psychiatric diseases[1]. The gut microbiota composition of an adolescent is usually simpler and more unstable when compared with that of an adult, which is highly diverse and stable[2,3]. These differences are probably due to relative. The initial microbiota is obtained during the birthing process and develops alongside its host from a rather

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Conclusion