Microbial metabolites in human newborns – future immunomodulatory agents for young and old

The first months of life represents a critical period for human immune system development1. Antibiotic exposure during this time perturbs microbial colonisation, derails the establishment of healthy immune-microbe relationships, and increases the risk of asthma and allergies2, autoimmune diseases like juvenile arthritis3, and even neurodevelopmental conditions like autism later in life1,3. Early in life the immune system must prevent pathogens from invading yet tolerate commensal microbes and avoid exuberant responses to harmless allergens. The detailed mechanisms involved in this balancing act are poorly understood but microbial metabolites are likely to be critical modulators4,5. Here we plan to search for microbial metabolites that modulate immune system development and investigate their mechanisms of action. We believe that better understanding of human immune development will help us develop new interventions that optimise this process and reduce risks of disease in all children in the future. Importantly, key microbial metabolites found in human newborns might also have potential as immunomodulatory agents beyond childhood, for example in adult patients with inflammatory diseases. Here I propose to combine the richness of a human birth cohort, with the potential of well-controlled in vitro systems to explore mechanisms by which microbial metabolites can modulate human immune systems.