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

Autism Res. 2019 Apr;12(4):576-588. doi: 10.1002/aur.2079. Epub 2019 Jan 25.

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.

Keywords: anti-inflammation; autism spectrum disorders; interleukin 17a; interleukin 6; maternal immune activation; probiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Autism Spectrum Disorder / prevention & control*
  • Behavior, Animal*
  • Disease Models, Animal
  • Female
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects / immunology
  • Prenatal Exposure Delayed Effects / prevention & control*
  • Probiotics / administration & dosage
  • Probiotics / pharmacology*