Fig. 3
From: Maternal elevated salt consumption and the development of autism spectrum disorder in the offspring
Maternal high salt diet and offspring ASD. Chronic consumption of high salt causes microbial dysbiosis in the maternal gut (A), which can then result in maternal immune system dysregulation: (a) increased differentiation of Th-17 cells and concomitant increased IL-17, (b) increased M1 macrophage activation with related cytokines and chemokines release, and (c) decreased Treg cell differentiation and regulatory M2 macrophage activation. The altered maternal gut microbiota and increased IL-17 travel via placental circulation to the fetus (B). In the fetal intestine, the gut microbiota and increasing IL-17 serum levels could cause a similar immune dysregulation as in the maternal side. When circulating IL-17 reaches the fetal brain and causes the activation of IL-17 receptor A (IL-17RA), several mechanisms can be triggered: (1) IL-17 could hamper the development of the fetal blood brain barrier (BBB), (2) reduction of the proliferation of neuronal stem cells (NSC) which in turn decreases neuro and gliogenesis, (3) dysregulation of the Act1 signaling pathway which alters the expression of ERK protein, and (4) IL-17 can also over-activate microglia. The described changes contribute to the ASD-like phenotype observed after birth (C)