Accumulating evidence indicates exposure to pesticides during the crucial neurodevelopmental period increases susceptibility to many diseases, including the neurodevelopmental disorder known as autism spectrum disorder (ASD). In the last few years, it has been hypothesized that gut microbiota dysbiosis is strongly implicated in the aetiopathogenesis of ASD. Recently, new studies have suggested that the gut microbiota may be involved in the neurological and behavioural defects caused by pesticides, including ASD symptoms. This review highlights the available evidence from recent animal and human studies on the relationship between pesticides that have the potential to disturb intestinal microbiota homeostasis, and ASD symptoms. The mechanisms through which gut microbiota dysbiosis may trigger ASD-like behaviours induced by pesticides exposure during the neurodevelopmental period via the altered production of bacterial metabolites (short chain fatty acids, lipids, retinol, and amino acid) are also described. According to recent research, gut microbiota dysbiosis may be a major contributor to the symptoms of ASD associated with pesticides exposure. However, to determine the detailed mechanism of action of gut microbiota on pesticide-induced ASD behaviours, actual population exposure scenarios from epidemiological studies should be used as the basis for the appropriate exposure pattern and dosage to be used in animal studies.

Epidemiological evidence indicates exposure to glyphosate-based herbicides (GBHs) increases the risk for autism spectrum disorder (ASD). The gut microbiota has been found to influence ASD behaviours through the microbiota-gut-brain axis. However, the underlying links between early life GBH exposure and ASD-like phenotypes through the microbiota-gut-brain axis remain unclear. Therefore, we exposed mice to low-dose GBH (0.10, 0.25, 0.50, and 1.00 %) and determined the effects on ASD-like behaviours. Furthermore, three kinds of omics (gut microbiomics, metabolomics, and transcriptomics) were conducted to investigate the effects of GBH exposure on gut microbiota, gut metabolites, and circular RNAs (circRNAs) in the prefrontal cortex (PFC) using a cross-generational mouse model. Behavioural analyses suggested social impairment and repetitive/stereotypic behaviours in the GBH-exposed offspring. Furthermore, maternal exposure to glyphosate significantly altered the ASD-associated gut microbiota of offspring, and ASD-associated gut metabolites were identified. Specifically, we found that alterations in the gut microenvironment may contribute to changes in gut permeability and the blood-brain barrier, which are related to changes in the levels of circRNAs in the PFC. Our results suggest a potential effect of circRNAs through the disruption of the gut-brain interaction, which is an important factor in the pathogenesis of ASD in offspring induced by maternal exposure to GBH.

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants found in various consumer products, such as drinking water, infant formula, and food, as well as in human biospecimens, including blood, urine, breastmilk, and cerebrospinal fluid. Previous evidence indicates that PFAS exposure poses significant neurotoxic risks, owing to their ability to penetrate the blood-brain barrier and bioaccumulate in neural tissue. The developing brains of fetuses and infants are particularly susceptible to the harmful effects of environmental pollutants because of their incomplete barrier and immune system development. This narrative review synthesizes current epidemiological and experimental evidence on the neurodevelopmental effects of PFAS exposure, with a primary focus on attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The available data, from both cross-sectional and prospective cohort surveys, indicate a potential link between PFAS exposure and the development of ADHD or ASD. Additionally, experimental studies demonstrate that PFAS exposure disrupts neurotransmitter regulation, induces oxidative stress and chronic neuroinflammation, and alters gut microbiota, all of which reflect key pathological features observed in both clinical and preclinical models of ADHD and ASD. The present narrative review also discusses current challenges and research directions aimed at elucidating the causal links between PFAS insults and the onset of ADHD or ASD. Notably, this review highlights the need for molecular epidemiological approaches and realistic exposure models in animal research to deepen our understanding of causal associations.