Impact of maternal microbiota imbalance during pregnancy on fetal cerebral neurodevelopment: Is there a link to certain autistic disorders?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with a heterogeneous group of psychiatric disorders primarily characterized by impairments in communication and social interactions. ASD typically emerges around 18 months of age. While no single etiology has been identified, theories suggest a combination of genetic predisposition and environmental factors, such as exposure to toxics, viral infections, and neuroinflammatory processes. However, the mechanisms linking environmental risk factors to ASD remain poorly understood, particularly during the prenatal period. Among the various hypotheses, the gut microbiota has been proposed as a potential modulator of nervous system development and function. During pregnancy, the maternal microbiota could trigger gestational inflammatory responses, leading to maternal immune activation (MIA). These deleterious processes could play a causal role in the etiopathogenesis of neurodevelopmental disorders in offspring. The gut microbiota could be the missing link between genetic susceptibility and environmental exposures in certain forms of ASD. The gut microbiome induces the production of microbiota-derived signaling metabolites, immune mediators, gut hormones, and neural signaling via the spinal cord and vagus nerve. This review synthesizes the current knowledge from preclinical rodent models and human studies that investigate the impact of the maternal gut microbiota during pregnancy on ASD risk in offspring. Additionally, the potential roles of the maternal oral and vaginal microbiota are also discussed in the context of this maternal-offspring pairing. Finally, we examine how restoring maternal microbiome balance, through interventions such as pre/probiotics, may help reduce the perinatal risk of certain ASD by positively influencing prenatal environmental factors.