Early-life gut microbiota depletion changes brain morphology and behaviour

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 [1]. 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 [2].

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.

1. Cowan CSM, et al. J Child Psychol Psychiatry. 2020;61:353–371.
2. 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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Posted on 28 November 2022