ArticleFrontiers in aging neuroscience2026
Stereoselective effects of nicotine enantiomers on the gut-brain axis and neuroinflammation in a mouse model of Parkinson's disease.
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration, neuroinflammation, and emerging evidence of gut microbiota dysbiosis. Although nicotine has been implicated in neuroprotection, whether its enantiomers exert stereoselective effects on the gut-brain axis remains unknown. Methods: We systematically compared the effects of S-nicotine and R-nicotine in an MPTP-induced mouse model of PD. Motor function, nigrostriatal dopaminergic neuronal loss, neuroinflammatory responses, intestinal barrier integrity, and gut microbiota composition were assessed. Results: Both enantiomers ameliorated motor deficits, attenuated nigrostriatal dopaminergic neuronal loss, and suppressed neuroinflammatory responses, yet exhibited markedly different efficacy profiles. S-nicotine produced robust neuroprotection at a lower effective dose (1 mg/kg), associated with improved motor performance, reduced central and peripheral inflammation, preservation of intestinal barrier integrity, and coordinated remodeling of the gut microbiota characterized by enrichment of Akkermansiaceae (notably Discussion: These findings demonstrate pronounced stereoselective and dose-dependent effects of nicotine enantiomers on neuroimmune modulation and identify gut microbiota remodeling as a functionally relevant correlate of nicotine-mediated neuroprotection in PD. Our results highlight the therapeutic potential of targeting the microbiota-gut-brain axis through chiral interventions and support S-nicotine as a promising candidate for neuroprotective strategies in aging-related neurodegenerative disorders.
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