Abstract
Maternal immune activation (MIA) increases the risk of autism spectrum disorder (ASD) in offspring. Microbial dysbiosis is associated with ASD symptoms. However, the alterations in the brain–gut–microbiota axis in lipopolysaccharide (LPS)-induced MIA offspring remain unclear. Here, we examined the social behavior, anxiety-like and repetitive behavior, microbiota profile, and myelination levels in LPS-induced MIA rat offspring. Compared with control offspring, MIA male rat offspring spent less time in an active social interaction with stranger rats, displayed more anxiety-like and repetitive behavior, and had more hypomyelination in the prefrontal cortex and thalamic nucleus. A fecal microbiota analysis revealed that MIA offspring had a higher abundance of Alistipes, Fusobacterium, and Ruminococcus and a lower abundance of Coprococcus, Erysipelotrichaies, and Actinobacteria than control offspring, which is consistent with that of humans with ASD. The least absolute shrinkage and selection operator (LASSO) method was applied to determine the relative importance of the microbiota, which indicated that the abundance of Alistipes and Actinobacteria was the most relevant for the profile of defective social behavior, whereas Fusobacterium and Coprococcus was associated with anxiety-like and repetitive behavior. In summary, LPS-induced MIA offspring showed an abnormal brain–gut–microbiota axis with social behavior deficits, anxiety-like and repetitive behavior, hypomyelination, and an ASD-like microbiota profile.
Highlights
Maternal immune activation (MIA) has been linked to an increased risk of neurodevelopmental psychiatric disorders in offspring [1,2]
We demonstrated that an abnormal brain–gut–microbiota axis with phenotypes includes a social behavior deficit, anxiety-like and repetitive behavior, hypomyelination, and dysbiosis microbiota in MIA offspring; providing a link between maternal infection and the etiopathogenesis of autism spectrum disorder (ASD)
MIA and control male offspring had no differences in the total distance moved, number of entries, or time spent in the wall zone of the open-field assay (Figure 1E)
Summary
Maternal immune activation (MIA) has been linked to an increased risk of neurodevelopmental psychiatric disorders in offspring [1,2]. Animal models of MIA have been developed by activating the immune system with immunogens during pregnancy and observing the development of defective behaviors in offspring with autism-like behavior [3]. MIA generates inflammatory cytokines to which the fetus is exposed during mid-gestation, possibly affecting fetal brain development [4]. Microbial dysbiosis is correlated with various adverse consequences, including behavioral abnormalities, neuropathology, immune dysfunction, and deficient gastrointestinal integrity [7]. Microbial dysbiosis is associated with the symptoms of autism spectrum disorder (ASD), including impaired social communication and repetitive behaviors [9]. How prenatal infection affects the brain–gut–microbiota axis, which regulates behavioral phenotypes, remains unclear
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