Gut microbiota play a critical role in long-term health by supporting metabolism, immune function, inflammation regulation, and neurological development via the gut–brain axis. Beneficial bacteria enhance gut integrity through short-chain fatty acid production, pathogen inhibition, and mucosal barrier support. However, microplastics (MPs) and nanoplastics (NPs) can disrupt microbiome development, particularly in infants. MPs may delay microbial stabilization and promote antibiotic resistance through biofilm-associated gene transfer. In neonates, especially those exposed to intensive care, antibiotics, or formula feeding, MPs/NPs present an added challenge to microbiome establishment. Probiotics offer a potential intervention by restoring microbial balance, strengthening gut barriers, and mitigating inflammation. Certain strains can bind or degrade environmental toxins, including MPs, heavy metals, and endocrine disruptors. Clinical studies support the use of probiotic mixtures to restore eubiosis. Given the limited availability of safe plastic alternatives in neonatal care, enhancing the gut microbiome through probiotics may help counteract the adverse effects of MPs/NPs. However, due to safety concerns—such as the FDA’s warning against live probiotics in preterm infants—future research should explore innovative, safe bioremediation strategies to support gut health in this vulnerable population.
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