The gut-brain axis in arsenic-induced toxicity: mechanisms, consequences, and therapeutic perspectives

Chronic ingestion of arsenic frequently occurring in contaminated groundwater poses a serious dual threat to neurological health. Environmental toxicants present in groundwater are highly correlated with onset of neuropathological effects through complex gut-brain axis interactions. The systematic review of literature aims evaluate the neurobehavioural consequences and molecular outcome of a groundwater contaminant, arsenic with microbiota alteration involving animal studies and epidemiological data. Arsenic disrupts the gut microbiota, diminishing beneficial bacteria and promoting harmful strains, which in turn compromise gut barrier integrity, trigger inflammation and oxidative stress, leading to alteration in critical metabolic pathways involved in neurotransmitter production and mitochondrial function. Animal studies have shown that chronic exposure intensifies these effects, causing more pronounced microbial dysbiosis alongside worsened cognitive and behavioural deficits. Mechanistically, arsenic impairs neural signaling by elevating reactive oxygen species, disrupting synaptic and mitochondrial dynamics, and inducing neuroinflammation after its accumulation in brain tissues, while gut-derived neuroactive compounds exacerbate neuroinflammation and neuronal damage irrespective of significant arsenic deposition in the brain. Therapeutic strategies that reinforce gut health, such as targeted probiotic and prebiotic supplementation have demonstrated the ability to restore microbiome balance, strengthen barrier function, reduce neuroinflammatory markers and improve behavioural outcomes in experimental models. These microbiota-focused interventions, when combined with conventional measures like chelation to remove toxic metals and the deployment of water treatment infrastructure in affected regions, suggest a powerful integrated approach. By addressing both the source of contamination and the downstream biological consequences, this multimodal strategy holds significant promise for mitigating arsenic-induced neurotoxicity and protecting at-risk populations in affected communities.