<p>Parkinson’s disease (PD) is a complex neurodegenerative disorder with evidence linking environmental factors, such as exposure to neurotoxins like mercury, to its pathogenesis. Recent research has increasingly highlighted the gut-brain axis as a potential pathway in PD development. This study aimed to investigate the potential association between chronic low-level mercury exposure, gut barrier dysfunction, and PD progression. A case series involving three Thai men with idiopathic PD and suspected mercury exposure was conducted. Blood samples were analyzed for mercury, lead, and other biomarkers. Food-specific immunoglobulin G (IgG) levels were assessed to evaluate gut barrier function. Clinical data including neurological assessments and disease progression were collected. All participants exhibited elevated total mercury concentrations, with two also having elevated blood lead levels. Food-specific IgG testing indicated gut barrier dysfunction. Oxidative stress, inflammation, and metabolic disturbances were evident, with varying degrees of severity across individuals. Notably, the patient with sustained metabolic dysfunction experienced the most significant disease progression. This case series suggests a potential association between chronic low-level mercury exposure, gut barrier dysfunction, and PD progression. Individual allostatic load, encompassing factors such as total toxin burden, inflammation, oxidative stress, and metabolic dysfunction, appears to influence disease course. These findings highlight the necessity of individualized treatment plans for PD patients, emphasizing the role of patient-specific factors beyond conventional risk profiles. However, given the study’s limitations, further research is needed to confirm these findings and elucidate the underlying mechanisms.</p>