Figure 1.

Novel evidence shows that the gut microbiota exert a strong influence over brain development, most likely via immune signaling, which might include soluble signals such as cytokines (TNF, IL-1, IL-6, and HMGB1 are highlighted) and chemokines as well as immune cells (dendritic cells, macrophages, T cells, and B cells are pictured). Notably, there is a “critical period” that is a developmental window during which the gut flora can influence the developing brain. Additionally, the mature brain exerts a strong influence on the immune system via the efferent arc of the vagus nerve. The right panel depicts the excitatory brain synapse as the most likely site of action for intrinsic immune-related mechanisms. The presynaptic axon releases glutamate into the synaptic cleft, which binds to glutamatergic receptors (AMPAR and NMDAR are pictured). The neighboring glia cells are responsible for glutamate reuptake and other processes. Studies have revealed the presence of receptors for cytokines in both glia and the neural elements of the synapse. It is, thus, hypothesized that cytokine levels induced by gut microbiota might influence the genesis and function of central synapses.