Bridging the Gap: The Potential Role of the Microbiota-Gut-Brain Axis in Linking Modern Industrial Xenobiotics to Neurological Disorders

The microbiota-gut-brain axis (MGBA) represents a bidirectional neuroendocrine system essential for maintaining metabolic and neurological homeostasis. While dietary macronutrients are known modulators of this axis, the cumulative impact of modern industrial xenobiotics remains insufficiently characterized. This review synthesizes contemporary, multidisciplinary evidence to elucidate how four ubiquitous environmental stressors Particulate Matter (PM2.5), Microplastics (MPs), Inorganic Nanoparticles (NPs), and Non-Nutritive Sweeteners (NNS) synergistically perturb this delicate enteric ecosystem. We integrate independent lines of research to propose a unifying pathological framework: these agents induce profound dysbiosis, significantly depleting beneficial, short chain fatty acid (SCFA) producing taxa (e.g., Lachnospiraceae, Faecalibacterium) and sharply diminishing the bioavailability of critical neuroactive mediators, including butyrate, GABA, serotonin, and indole derivatives. Concurrently, NNS-driven bacteriostatic shifts, the MP “plastisphere” phenomenon, and NP-induced oxidative mucosal abrasion critically compromise the intestinal barrier. This “leaky gut” facilitates the unrestricted systemic translocation of lipopolysaccharides (LPS) and trimethylamine-N-oxide (TMAO), driving a peripheral Treg/Th17 immune imbalance that propagates via the gut-liver and gut-heart axes directly to the central nervous system (CNS). Crucially, the synthesis of this data points toward a potential “Dual-Hit” mechanism, suggesting that these xenobiotics aggravate neurological pathology through simultaneous mechanisms: acting as direct neurotoxicants via CNS translocation (e.g., NPs crossing the blood-brain barrier to trigger epigenetic reprogramming and amyloid aggregation) while concurrently driving “bottom-up” systemic neuroinflammation. By linking these disruptions to classic neurodegeneration (Alzheimer’s, Parkinson’s) as well as underexplored pathologies (migraine, epilepsy, restless leg syndrome, and substance use disorders), this review underscores the urgent need for a paradigm shift in environmental neurotoxicology and the development of targeted microbiome-based interventions.