4M: Microbes, Milk, Mental Health and Me; how do early life gut microbiota and feeding shape long-term mental health in the C-GULL Cohort? (360G-Wellcome-226630_Z_22_Z)

The global burden of mental health conditions is a profound public health challenge, worsened by the COVID-19 pandemic, and yet we know little about their early-life origins. Compelling evidence points towards microbial gut colonisation, strongly influenced by breastmilk, as an important determinant of neurodevelopment trajectories and mental well-being via the microbiota-gut- brain axis, but there is little definitive research on the mechanisms. To help close this knowledge gap, we propose ‘4M: Microbes, Milk, Mental Health and Me’ – enhancing the Children Growing up in Liverpool (C-GULL) programme by enabling collection of additional bio-samples, state-of-the-art gut microbiota and breastmilk profiling, and rigorous mechanistic exploration of the causal pathways underlying adverse mental health outcomes in this richly-phenotyped birth cohort. We will generate, integrate, and interrogate large-scale genomic and epidemiological datasets to perform experimental testing, biological discovery, causally robust epidemiology, and translational science. We will also create an internationally unique archive of paired bio-samples from mothers and babies and identify keystone bacteria and milk constituents that influence neurodevelopment and mental health. This will generate robust evidence for preventative and therapeutic interventions (e.g., diet, Live Bacterial Therapeutics) to restore and select for age-appropriate beneficial species to optimise a child’s resistance to adverse mental health conditions.