Background: The gut-brain axis (GBA), also known as the gut-brain-microbiota axis, is the bi-directional communication between the gastrointestinal environment and the brain, with the gut microbiota playing a central role. This connection is increasingly recognized as a key factor in the pathophysiology of Parkinson’s disease (PD). Diet influences the gut microbiota composition and function, but results from previous studies on healthy dietary patterns and PD risk are inconsistent. Most of the studies focused on single nutrients or food groups, though assessing overall dietary patterns may better reflect the combined effects of various foods on PD risk. In the Swedish Mammography Cohort and Cohort of Swedish Men, we found that higher intake of vitamin E and beta-carotene was associated with lower PD risk, but not vitamin C or total antioxidant capacity. Adherence to Mediterranean or Mediterranean-DASH Intervention for Neurodegenerative Delay diets has also been associated with better PD outcomes. The ketogenic diet, characterized by high fats, moderate proteins and very low carbohydrates, has also shown potential benefits for PD. In the Women’s Lifestyle and Health Study, we found lower PD risk with high adherence to the Mediterranean diet, though the study was limited by its all-female, relatively young cohort and lack of repeated dietary assessments. Aim and hypothesis: We aim to evaluate the association between adherence to a Mediterranean dietary pattern or an anti-inflammatory diet and the risk of developing PD. Based on available evidence on the associations between Mediterranean and Western dietary patterns and microbiome composition, we hypothesize that Mediterranean and anti-inflammatory dietary patterns are both related to a lower risk of developing PD. Methodology: We plan to conduct a prospective cohort study in SIMPLER. Participants responded to detailed questionnaires about diet and a large range of other lifestyle factors in 1987-1990 (women), 1997, 2008, and 2009. We will use the 1997 questionnaire as the baseline (38,984 women and 45,906 men), as this is the first year including dietary information for both cohorts. PD-free individuals will be followed from baseline until the end of follow-up. We will assess Mediterranean diet adherence by the modified Mediterranean diet score (mMED). The anti-inflammatory potential of the diet will be assessed by the anti-inflammatory dietary index (AIDI), which has been developed empirically and validated against serum high-sensitive CRP measurements in a subcohort of SIMPLER. We will use Cox proportional hazards regression to assess the relationship between adherence to healthy dietary pattern (Mediterranean diet and anti-inflammatory dietary index) and risk of PD, adjusting for attained age, sex, energy intake, alcohol, coffee, smoking, education, physical activity, BMI and comorbidities; dietary indices will be categorized in quartiles. Furthermore, we plan to use the repeated food frequency questionnaire measurements at time points 2009 and 2019 to perform a longitudinal analysis.