Depletion of gut microbiota during critical windows of development induced changes in the corticolimbic system by altering key neuromodulators of the gut-brain axis signalling and eventually led to alterations in brain physiology and behaviour, a study in mice showed.
Numerous studies have emphasised the importance of the gut microbiota during early life and its role in modulating neurodevelopment and behaviour. Its developmental trajectory coincides with key critical windows of neural development and the onset of mental disorders such as autism spectrum disorder, ADHD, and schizophrenia . PhD student Caoimhe Lynch (University College Cork, Ireland) investigated the impact of targeted antibiotic-induced gut microbiota depletion during critical developmental windows and the long-term behavioural effects .
The researchers administered a cocktail of oral antibiotics to mice in 3 different critical windows of their development: postnatal, pre-weaning, and post-weaning. The long-term effect of this intervention was studied when the mice reached adolescence.
The antibiotic treatment during early life dramatically altered the gut microbiome in adolescence, as was observed in differences in alpha and beta diversity (richness and amounts of bacteria) between vehicle- and antibiotic-treated mice. In addition, alpha and beta diversity differed between the post-natal, pre-weaning, and post-weaning treated mice. In general, antibiotic treatment favoured potentially pathogenic bacteria, like E. coli and Staphylococcus, and decreased the presence of short-chain fatty acid-producing bacteria, like Bacteroides. Furthermore, microbial-derived gut metabolites that play a role in neurologic development and neuroactive compounds were found to be altered by early-life antibiotic treatment. In line with this, microglial morphology in the basolateral amygdala of adolescent mice was found to be altered by early-life microbiota disruption. Of note, myelin gene expression in the prefrontal cortex was altered only in female mice treated with antibiotics in the pre-weaning window.
Regarding behaviour, adolescent female mice treated with antibiotics in the pre-weaning window demonstrated increased anxiety in an open field test. No significant effects of microbial disruption were observed in depressive-like, social, or memory-related behaviours.
“Overall, this study highlights the vulnerability of the gut microbiota during critical windows of development. Early-life microbiota depletion may induce subtle changes in the corticolimbic system by altering key neuromodulators of gut-brain axis signalling, eventually leading to alterations in brain physiology and behaviour,” concluded Ms Lynch.
- Cowan CSM, et al. J Child Psychol Psychiatry. 2020;61:353–371.
- Lynch CMK, et al. Sex dependent effects of early-life microbiota depletion on behaviour, neuroimmune function and neuronal development. Abstract S10.05, ECNP Congress 2022, 15–18 October, Vienna, Austria.
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Table of Contents: ECNP 2022
Letter from the Editor
Zuranolone shows rapid-acting efficacy in postpartum depression
Probiotics could reduce perceived stress
KarXT is effective in schizophrenic patients experiencing acute psychosis
Low-dose ulipristal acetate is an effective treatment for PMDD
Endogenous oxytocin release helps the mind to deal with pain
Nitric oxide synthase genetic variant is a risk factor for suicidal behaviour
Early-life gut microbiota depletion changes brain morphology and behaviour
Treating intrusive memories after trauma in healthcare workers using Tetris
VR exposure as effective as in vivo exposure for phobia
Efficacy of smartphone-based treatment of bipolar disorders not (yet) validated
Mode of action of psilocybin
Fast and sustained effect of 2 administrations of psilocybin on depression
Antidepressant properties of psilocybin might be related to changes in sleep
Both sex hormones and serotonin play a role in peripartum mental health
Child loss induces short- and long-term neurobiological changes
Reproductive state matters when looking at the female brain and drug treatment effects
Different brain responses to fat and/or sugar
Diabetes not related to abnormal biomarkers of Alzheimer’s disease
Oxytocin treatment induces long-lasting neurobiological adaptations in autism
Novel approaches to understanding the social brain