Maternal immune activation and antibiotics affect offspring neurodevelopment, behaviour, and microbiome

In utero exposure to an increased level of maternal inflammation or a disrupted maternal gut microbiome during pregnancy have been linked to several neurodevelopmental disorders in the offspring. Despite the strong links between these two adverse events, few studies looked at the interaction between the maternal gut microbiome and maternal immune activation (MIA) on the neurodevelopmental outcomes in the offspring. Here, we aim to determine if maternal gut microbiome disruption exacerbated the impact of systemic inflammation on brain development, offspring behaviour, and long-term microbiome changes. A low dose of intraperitoneal lipopolysaccharide (LPS) was administered to pregnant Sprague Dawley rats from gestational day 12-18. Concurrently, an antibiotic cocktail (ampicillin, neomycin, vancomycin) was given in the drinking water to disturb the maternal microbiome. Embryos at gestational day 18 were found to have a reduced body size and weight, along with reduced placental weight following exposure to LPS, with some effects also seen with antibiotic exposure. Offspring exposed to LPS in utero were found to have increased anxiety-like behaviours and repetitive-behaviours. No behavioural changes were noted from antibiotic exposure. The expression of 5HT1a receptors in the prefrontal cortex was found to be reduced following LPS exposure. The offspring microbiome varied between the groups, with prenatal antibiotic exposure playing a role in reducing α-diversity and species richness in the periadolescent period. This study highlights the impact of prenatal exposures on different aspects of neurodevelopment. However, additional research is warranted to explore the role of the maternal immune system and microbiome on the offspring development, while also testing the potential therapeutic agents such as probiotics.