Figure 1.

Gut microbiota influences microglial development and maturation. (A) Microglial maturation states can be described in three primary phases: early, pre-, and adult microglia. Each phase of development can be defined by expression of a subset of genes that correspond to a core set of microglial functions. Early and premicroglia have two main functions during early brain development: synaptic remodeling and subsequent shaping of neural circuitry and regulating the number of neurons through mechanisms of programmed cell death (PCD). A few weeks after birth, microglia transition to the “adult microglia” stage, in which they constantly survey their immediate surroundings and actively maintain homeostatic conditions. In the presence of tissue damage or an immune stimulus, microglia activate pro- and anti-inflammatory signaling cascades to clear pathogens and repair tissue damage to restore brain health. Recent evidence suggests that prenatal and postnatal inputs from the gut microbiota are critical for microglial maturation and function. (B) In SPF mice, a diverse gut microbiota promotes microglial development and maturation. Microglial development appears arrested in GF mice, as supported by high expression of genes characteristic of early and premicroglia in microglia from adult GF mice. This arrest in microglial maturation impedes their ability to initiate a sufficient immune response during infection. EMP, erythromyeloid progenitor.