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Prebiotic Treatment During Pregnancy Prevents Social Deficits Associated with Autism Spectrum Disorder-like Behavior
Frederico Rogério Ferreira1,2, Guilherme Araujo Rouvier1, Lucas Hassib1,3
1Oswaldo Cruz Foundation, Oswaldo Cruz Institute, Rio de Janeiro 21040-360, RJ, Brazil.
Insights
Maternal immune activation during pregnancy may harm offspring neurodevelopment. Inulin supplementation during pregnancy protected offspring from social deficits and anhedonia, suggesting a potential protective role via microbiome modulation.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Maternal exposure to infectious agents is linked to offspring mental disorders like autism spectrum disorder.
- Maternal immune responses during pregnancy can impact fetal neurodevelopment and future central nervous system function.
- Inulin, a prebiotic fiber, promotes beneficial short-chain fatty acids and may reduce inflammation.
Purpose of the Study:
- To investigate if inulin treatment during pregnancy can mitigate the effects of maternal immune activation (MIA) on offspring neurodevelopment.
- To assess the protective effects of inulin against maternal exposure to soluble *Toxoplasma gondii* antigen (STAg) in a mouse model.
- To analyze behavioral outcomes and gut microbiota changes in offspring following maternal inulin treatment and immune challenge.
Main Methods:
- A dose-response study using Swiss mice exposed to STAg and varying doses of inulin during pregnancy.
- Behavioral assessments of adult offspring, including the three-chamber social interaction test and anhedonia tests.
- Characterization of offspring fecal microbiota composition at family and genus levels.
Main Results:
- Offspring exposed to STAg exhibited reduced sociability (males and females) and anhedonia (females only).
- Inulin co-treatment significantly mitigated STAg-induced social deficits and anhedonia in offspring.
- Significant alterations in fecal microbiota composition were observed between STAg-exposed and inulin-treated groups.
Conclusions:
- Inulin demonstrates a potential protective effect against neurodevelopmental impacts of maternal immune challenges during pregnancy.
- The protective mechanisms of inulin may involve modulation of the offspring's gut microbiome.
- Inulin supplementation represents a promising strategy to counteract adverse neurodevelopmental outcomes linked to maternal immune activation.
Abstract:
Maternal exposure to infectious agents has been associated with an increased risk of mental disorders in offspring, such as autism spectrum disorder. Evidence suggests that maternal immune responses during infection can significantly impact the neurodevelopment of the offspring, potentially affecting central nervous system functions in the future. Inulin is an indigestible soluble fiber that acts as a prebiotic. It promotes the production of short-chain fatty acids, such as butyrate, which can help inhibit the production of pro-inflammatory cytokines. Thus, this study aims to investigate whether inulin treatment during pregnancy can mitigate or reduce the impact of maternal immune activation (MIA) on the neurodevelopment of the offspring. Swiss mice were used in a dose-response study to evaluate the protective effects of inulin against maternal exposure to soluble Toxoplasma gondii antigen. Adult offspring of both sexes underwent behavioral assessments, and their gut microbiota was characterized. Both males and females in the soluble T. gondii antigen (STAg) group exhibited reduced sociability, as evidenced by the three-chamber social interaction test. Moreover, co-treatment with inulin mitigated this effect. Additionally, anhedonia was observed only in female offspring from the MIA group, but treatment with 1% and 3% inulin also mitigated this effect. The analysis of fecal microbiota showed significant differences between the STAg and inulin treatments at both the family and genus levels. Therefore, inulin appears to have a potential protective effect on the neurodevelopment of the offspring exposed to maternal antigenic challenges during pregnancy mediated by offspring microbiome modulations.
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