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Gut microbiota-Microglia Interactions in NeuroDevelopment

Periodic Reporting for period 1 - GutMIND (Gut microbiota-Microglia Interactions in NeuroDevelopment)

Okres sprawozdawczy: 2018-06-01 do 2020-05-31

Childhood psychiatric disorders are alarmingly common, but there remain many unknowns about how they start, what factors can contribute to their onset or maintenance, and the best ways to treat them. There is a long history of research showing that certain points of early life (known as “critical windows”) are particularly important for normal development of the brain and behaviour. However, not all the contributing factors are well-defined. The GutMIND project asked whether interactions between the brain and the body, and especially the bugs living in our guts (the “gut microbiome”), have critical windows. We tested whether microbiome disruption by antibiotics during early life has implications for neural and behavioural outcomes in mice. This is particularly important to understand given the high rates of antibiotic use in modern society; antibiotics not only kill harmful bacteria but also deplete the microbiome, with little known about the collateral impact on our brains and behaviour, especially in developing individuals. Our results addressing these questions will be published soon.
We used a mouse model to test whether the microbiome is more or less important during very specific times of development. We treated mice with antibiotics during these specific time windows, then observed their behaviour in a series of tasks that test a wide range of abilities and behaviours. We tested both males and females, and examined behaviour in both adolescence and adulthood to look for potential sex effects and to capture the full timeline of possible impacts of the microbiome depletion. There were only subtle effects of early-life microbiome depletion on later behaviour, with ongoing work examining potential antibiotic-induced changes in brain function. Once our results have been through the scientific peer review process, we aim to share them with doctors and parents through our social media platforms, public events, and collaborators in hospitals. This will mean that these groups have the most up-to-date information to help them make informed decisions about using antibiotics in early life.
We moved beyond previous research by examining the effects of early-life antibiotics in both male and female animals in our mouse model. We were the first to compare very specific and targeted windows of microbiome depletion in early life, with the aim of better understanding the timeline of microbiome interactions with the brain. This provides us with valuable information on the later consequences of these important, often life-saving, medical interventions.
Does microbiome disruption by antibiotics impact neural and behavioural development?
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