Mapping intestinal neuro-immune-microbiota communications at birth, and their lifelong immunological impact

The infant gut undergoes massive microbial colonization at birth, which is crucial for proper development of intestinal and systemic immunity. Recent studies suggest that alterations to gut microbiota composition in early life, are linked to disease development later in life. However, the molecular mechanisms that facilitate proper host-microbiota interactions at birth remain mostly unknown.

To analyze these interactions, we have developed an intestinal organ culture system that preserves the physiologic tissue structure and cellular complexity. This advantage facilitates experimentations which cannot be reliably performed in-vivo, and has already led us to discover some unexpected roles for enteric neurons in mediating microbiota-induced effector and regulatory T-cells (Treg) development.

Based on these findings, we hypothesize that the enteric nervous system mediates immune-microbiota interactions at birth, and that these early neuro-immune-microbiota communications impact T-cells development and disease susceptibility later in life. To address this hypothesis, we utilize the gut organ culture system to systemically map the intestinal neuro-immune responses to neonatal microbiota at birth, and to determine whether alterations to neonatal microbiota composition in mice and humans disrupt early-life intestinal responses.

Our preliminary work established the use of the gut organ culture system as a valuable tool for dissecting host-microbiota interactions at birth. We expect that this transformative experimental approach will provide novel insights into neuro-immune-microbiota interaction at birth, and their long-term immunological impact