Microbiota depletion in adolescence induces permanent neurobehavioral changes in adulthood
The role of gut microbiota through the gut-brain axis in neurological functions regulation and brain health recently gained extensive interest in various research fields. Several studies have demonstrated that an equilibrium shift in this bidirectional communication could have long-lasting effects on brain health and behaviour.
Adolescence is a vulnerable period in which brain is highly responsive and promote maturation of social behaviour, emotional and cognitive capabilities and is also a crucial moment for the onset of psychiatric diseases. During this phase, the microbiota is simple and unstable, showing an immaturity which makes it more sensitive to environment and stress factors, such as diet or antibiotics (ABX). In particular, antibiotics are largely used during the adolescent period, for example for acne management, and this could alter gut microbiota composition and affect behavioural parameters, increasing the susceptibility to develop neuropsychiatric disorders.
In this study, Lach and colleagues investigated the effects of microbiota depletion with antibiotics in adolescence and in adulthood, highlighting the vulnerability of gut microbiota and the importance of its preservation during development.
In order to verify if enduring shifts in the microbiota composition could be due to a perturbation at a timepoint, adolescent and adult mice were treated with an ABX cocktail for three weeks. After the treatment, anxiety-like behaviours, memory, sociability and fear conditioning were evaluated.
Results showed that adolescent mice treated with ABX had long-lasting effects in the composition and structure of the microbiota, an increased anxiety-like behaviour and showed changes in gene expression in the amygdala, whereas adult mice had no effects. This demonstrated that the long-lasting effects only occur when mice were treated during a critical developmental period. Moreover, evidences suggest that changes in microbiota composition may affect sexual hormone production, which have a larger impact during the adolescence. In addition, microbiota depletion can increase inflammatory responses and facilitate peripheral substances to potentially reach the brain through the bloodstream. No effects were observed on memory, fear conditioning or social behaviour. Interestingly, ABX treatment seems to play a role in myelin-related gene both in adolescent and in adult mice, indicating that gut microbiota depletion does not affect myelination only during critical development periods but also in adulthood.
Taken together, these data highlight the vulnerability and the importance of gut microbiota at a timepoint in which several neuronal functions are developing and the long-lasting impact that microbiota depletion could have on gene expression and behaviour in adulthood. Moreover, this study supports the need for further investigations on long-term effects of antibiotics on microbiota composition and associated risks to the brain functions and neurobehaviour.