The Impact of Short-Chain Fatty Acids on Neonatal Regulatory T Cells

Over the first weeks of life, the neonatal gastrointestinal tract is rapidly colonised by a diverse range of microbial species that come to form the 'gut microbiota'. Microbial colonisation of the neonatal gut is a well-established regulator of several physiological processes that contribute to immunological protection in postnatal life, including the development of the intestinal mucosa and adaptive immunity. However, the specific microbiota-derived signals that mediate these processes have not yet been fully characterised. Accumulating evidence suggests short-chain fatty acids (SCFAs), end-products of intestinal bacterial metabolism, as one of the key mediators of immune development in early life. Critical to neonatal health is the development of regulatory T (Treg) cells that promote and maintain immunological tolerance against self and innocuous antigens. Several studies have shown that SCFAs can induce the differentiation and expansion of Tregs but also mediate pathological effects in abnormal amounts. However, the exact mechanisms through which SCFAs regulate Treg development and pathologies in early life remain poorly defined. In this review, we summarise the current knowledge surrounding SCFAs and their potential impact on the neonatal immune system with a particular focus on Tregs, and the possible mechanisms through which SCFAs achieve their immune modulatory effect.