Oral probiotic administration during pregnancy prevents autism‐related behaviors in offspring induced by maternal immune activation via anti‐inflammation in mice

Abstract

Maternal immune activation (MIA) is associated with an increased risk for autism spectrum disorders (ASD) in offspring. Animal experiments have found that interleukin 6 (IL‐6) and IL‐17a are key cytokines in the induction of ASD by MIA. Moreover, probiotics were verified to inhibit the production of proinflammatory cytokines. Therefore, we investigated whether the administration of oral probiotics during pregnancy might protect the offspring that have suffered MIA from developing ASD. Probiotics were orally administered to pregnant mice with/without the simultaneous administration of Poly(I:C). We found that oral probiotics prevented the ASD‐like behaviors induced by MIA in offspring. Furthermore, oral probiotics prevented the MIA‐induced increases in the IL‐6 and IL‐17a levels in both maternal serum and fetal brains, parvalbumin positive (PV+) neuron loss, and the decrease in the γ‐aminobutyric acid levels in the prefrontal cortex of adult offspring. This work suggests that administering oral probiotics during pregnancy may help decrease the risk of ASD following MIA during pregnancy. Autism Res 2019, 12: 576–588. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Interleukin 6 (IL‐6) and IL‐17a are key cytokines in the maternal immune activation (MIA)‐induced autism spectrum disorders (ASD). Based on emerging evidence that probiotics can inhibit the production of proinflammatory cytokines, we found that oral probiotics prevented MIA‐induced ASD‐like behaviors in offspring. This work suggested that oral probiotics during pregnancy may be an effective means for decreasing the incidence of ASD in offspring.

Brain Structural and Functional Alterations in Mice Prenatally Exposed to LPS Are Only Partially Rescued by Anti-Inflammatory Treatment

“…Several studies in the literature report the protective effect of the treatment with anti-inflammatory drugs on MIA models, but most of them have been performed on the offspring [ 31 , 84 , 85 , 86 , 87 ]. Only a few studies have been conducted on dams, but not using pharmacological treatment with anti-inflammatory drugs [ 88 , 89 , 90 , 91 ].…”

“…In the field of neuropsychiatry, the idea that alteration of minicolumnar cortical structure and function (minicolumnopathy) may be responsible for aberrant brain function is growing [ 66 , 70 , 92 ]. Minicolumns are basal and functional units of the brain cortex and minicolumnopathies are modifications of minicolumnar homeostasis induced by various factors, such as neuroinflammation, gene expression or environmental factors, typically present in several NDDs [ 89 , 90 , 91 , 92 ]. We demonstrated, for the first time, that LPS prenatal exposure induces aberrant brain cytoarchitecture.…”

The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders

“…In the same context, a study conducted by Wang et al showed that oral probiotic administration during pregnancy prevents autism-related behaviors in offspring. It has been shown in this study that the administration of 1.5675 × 10 7 cfu Bifidobacteria (B. bifidum and B. infantis) and 5.28 × 10 8 cfu Lactobacillus helveticus every 24 h for 21 days in addition to prebiotics (fructooligosaccharides (FOS) and maltodextrin) decreases the incidence of ASD in offspring and inhibits the production of proinflammatory interleukin 6 (IL-6) and IL-17a, which are key cytokines in the induction of ASD by maternal immune activation [165].…”

Could Gut Modulation through Probiotic Supplementation Be Beneficial in Autism Spectrum Disorder?

“…A role for probiotics has been suggested for children with ASD as well, as preliminary findings from experimental animals studies provide some evidence that administration of selected probiotics may be effective in reducing neurologic signs and symptoms associated with gut dysbiosis. In a summary of studies to date, several probiotic strains, i.e., [18,[89][90][91][92]. In a mouse model of ASD induced by maternal immune activation, oral administration of human commensal B. fragilis corrected intestinal permeability, restored GM, improved GI physiology, and abolished ASD-like behavioral disruptions [18].…”