Bacterial Peptidoglycans from Microbiota in Neurodevelopment and Behavior

The gut microbiota has emerged as a key regulator of brain development and behavior. However, the mechanisms mediating the interactions between the microbiota and the developing brain are still poorly understood. The central activation of PRRs by bacteria-derived products such as PGN (a major component of the bacterial cell wall) could represent a potential pathway affecting the developing brain and behavior. PGN-sensing molecules are abundantly expressed in the placenta and developing brain during specific time-windows of perinatal development, and have been implicated in the regulation of social behavior and anxiety, as well as in behavioral responses to stress. PGN and its sensing molecules represent an attractive biological pathway for the development of novel biomarkers and therapeutic strategies for neurodevelopmental and psychiatric disorders. It is increasingly recognized that the gut microbiota profoundly influences many aspects of host development and physiology, including the modulation of brain development and behavior. However, the precise molecular mechanisms and signaling pathways involved in communication between the microbiota and the developing brain remain to be fully elucidated. Germline-encoded pattern-recognition receptors (PRRs) that recognize conserved microbial molecular signatures such as bacterial surface molecules (e.g., peptidoglycans, PGNs) have emerged as potential key regulators of gut microbiota–brain interactions. We highlight current evidence supporting multiple and essential roles for PGNs and their sensing molecules beyond innate immunity, extending to neurodevelopment and behavior. In addition, the possible implications of the PGN signaling pathway for the pathogenesis of neurodevelopmental disorders such as autism spectrum disorder (ASD) are considered. It is increasingly recognized that the gut microbiota profoundly influences many aspects of host development and physiology, including the modulation of brain development and behavior. However, the precise molecular mechanisms and signaling pathways involved in communication between the microbiota and the developing brain remain to be fully elucidated. Germline-encoded pattern-recognition receptors (PRRs) that recognize conserved microbial molecular signatures such as bacterial surface molecules (e.g., peptidoglycans, PGNs) have emerged as potential key regulators of gut microbiota–brain interactions. We highlight current evidence supporting multiple and essential roles for PGNs and their sensing molecules beyond innate immunity, extending to neurodevelopment and behavior. In addition, the possible implications of the PGN signaling pathway for the pathogenesis of neurodevelopmental disorders such as autism spectrum disorder (ASD) are considered.