Immune Pathways:
Both the CNS and the gut microbiota directly affect, and are affected by, the immune system
The microbiota is also necessary for healthy development, maturation and activation of microglia, innate immune cells of the brain
The gut microbiota and the brain also interact through the systemic immune system via circulating cytokines. Changes to systemic immunity drive altered immune signalling within the brain and increased peripheral inflammation is found in many neuropsychiatric diseases, including depression, anxiety and ASD.
Cytokines and chemokines can either be produced by brain-resident immune cells or access the CNS through direct transport across the BBB. Importantly, there is evidence that the permeability of the BBB is influenced by the gut microbiota, as some reports show that GF mice have increased BBB permeability relative to control mice, partially due to reduced expression of tight-junction proteins such as occludin and claudin. Infections, autoimmune disease and injury can alter BBB integrity, thus increasing accessibility of the brain to microbial products in the circulatory system and sensitising the brain to subsequent pathology.