There is an increasing appreciation of the important role that prenatal maternal stress plays in shaping foetal brain development and influencing neurodevelopmental functioning. Altered maternal neuro-immune interactions along the microbiota-gut-brain axis may significantly influence neurodevelopmental outcomes but the precise mechanisms underpinning these effects are poorly understood.
Stress induced changes in gastrointestinal (GI) permeability can produce a peripheral pro-inflammatory phenotype in the mother. This in turn may lead to altered metabolism of the essential amino acid tryptophan along the kynurenine pathway. Downstream metabolites of the kynurenine pathway, kynurenic acid and quinolinic acid can modulate cholinergic and glutamatergic central nervous system (CNS) activity, respectively potentially having potent effects on pre and postnatal CNS development and function.
In this study we propose to determine if altered tryptophan metabolism is a conduit though which the physiological consequences of prenatal maternal stress (abnormal HPA axis function, a microbiota-driven increased permeability of the GI tract, immune activation) can converge to impact on pre and postnatal brain development.
To do so, we will utilise biological samples in tandem with neurodevelopmental and brain imaging (fMRI) data from two ongoing large prospective cohort studies; the IMPROvED study (http://www.fp7-improved.eu/) and the FinnBrain Project (www.finnbrain.fi). By identifying a biological signature of vulnerability to prenatal maternal stress and associated adverse neurodevelopmental outcomes, it is envisaged that the benefits of this study will be manifold and will inform suitable intervention strategies such as stress reduction techniques or microbiota targeted nutritional approaches directed towards improving GI permeability.
