Early-life microbiota dysbiosis as a link between Autism Spectrum Disorder and Parkinson’s Disease

Autism spectrum disorder (ASD) arises from a complex interplay of genetic and environmental factors that disrupt early brain development.Heritability exceeds 80%, with contributions from rare de novo mutations, common polygenic variants, and prenatal exposures (e.g., maternal infection, heavy metals, or herbicides) collectively altering synaptic connectivity and neural circuit formation [1,2].Clinically, ASD typically emerges before age two, manifesting as delays or atypicalities in social communication alongside restricted, repetitive behaviors or sensory sensitivities.Although core symptoms often persist, early intervention, comorbidities (such as intellectual disability or epilepsy), and tailored supports can significantly improve language, social skills, and adaptive functioning, whereas others may continue to require lifelong assistance.In this commentary, we propose a mechanistic link between early-life gut microbiota dysbiosis in ASD and longterm vulnerability to Parkinson's disease (PD), and outline key directions for future epidemiological and interventional studies.To explore the possibility that ASD predisposes to neurodegenerative disorder PD in later life, we next examined epidemiological links with PD.Although ASD has traditionally been viewed as a purely neurodevelopmental disorder, reports of degenerativelike changes in the brains of individuals with ASD raises the possibility that early developmental disturbances may predispose individuals to later neurodegeneration [3].A recent nationwide, population-based cohort study of 2278,565 individuals (33.9 million person-years) found that PD occurred in 0.05% of those with ASD versus 0.02% of those without, yielding a relative risk of 4.43 (95% CI, 2.92-6.72)that persisted after adjusting for sex, socioeconomic status, family history, and age at ASD diagnosis [4].Preterm or early-term birth did not modify this risk, whereas depression and antidepressant use roughly doubled PD risk independently of ASD (RR 2.01; 95% CI, 1.40-2.88),and antipsychotic exposure partially attenuated but did not eliminate the association (RR 2.00; 95% CI, 1.27-3.14).These data point to a shared vulnerability spanning neurodevelopmental and neurodegenerative processes.However, a relative risk of 4.43 reflects an epidemiological association-not proof of causation.Yet this link underscores the need for targeted mechanistic studies-such as longitudinal gut-microbiome profiling, in vivo models of synuclein propagation, and integrated immune-metabolite analyses-to elucidate pathways along the gut-brain axis.Emerging data implicate gut microbiota dysbiosis in both ASD and PD.In ASD, reduced microbial diversity, lower levels of