Impact of Diet on the Microbiome-Immune-Brain Axis in Parkinson's Disease

"Impact of Diet on the Microbiome-Immune-Brain Axis in Parkinson's Disease" as Part of the Collaborative Research Center 1697 "Targeting the Microbiome-Immune-Brain Interaction in Neurodegeneration"

Habitual adherence to a predominantly plant-based diet, rich in low-processed food (LPF) has been associated with a reduced risk for development and slower progression of Parkinson's Disease (PD). This could be due to neuroprotective effects by modulation of the gut microbiota and decreased neuronal and metabolic inflammation. So far, the effect of a predominantly plant-based LPF-diet on the microbiome-immune-brain axis in patients with PD remains unknown. In addition, the influence of dietetic measures on the gut microbiome is variable and may depend on (long-term) adherence as well as on PD-specific factors and lifestyle.

The investigators hypothesize that compared to an average German diet, the predominantly plant-based New Nordic LPF-diet, as a culturally adapted diet, which is rich in fermentable fiber and phytochemicals, will have beneficial effects on the gut microbiome of patients with PD by increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria (primary outcome) and will improve gut motility, metabolic resilience, and inflammation (secondary outcomes). Furthermore, the investigators postulate that a patient-centered dietary intervention program, including a multifaceted patient education and supported by a web-application, will lead to high adherence as a key determinant of long-term changes in the gut microbiome. This dietary intervention will be accepted by patients as a low-threshold treatment that balances personal benefits, therapeutic barriers and ethical concerns of early risk disclosure in PD.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Behavioral: 8 week predominantly plant-based New Nordic LPF-diet program; Behavioral: maintenance of the predominantly plant-based New Nordic LPF-diet

Detailed Description

In a pilot-intervention study, our project will:

• develop a practical, low-threshold diet intervention for patients with prodromal and clinical PD. Adherence will be promoted (i) by a patient-oriented approach, (ii) by implementation of the predominantly plant-based New Nordic LPF-diet that is scientifically-based, culturally adapted, sustainable and culinary and (iii) by an innovative web-application.
• investigate the acute effects of the predominantly plant-based New Nordic LPF -diet on the microbiome (abundance of SCFA-producing bacteria), gastrointestinal motility, inflammation as well as metabolic and Parkinson-specific clinical outcomes in individuals with prodromal and clinical PD.
• investigate potential determinants of long-term changes in the gut microbiome (e.g. dietary adherence, gastrointestinal motility, meal timing and frequency), and factors associated with a high adherence (e.g. acceptance of diet as therapeutic intervention in the prodromal phase, health-related quality of life).

The patient-centered intervention program will be tailored to individual needs and preferences of individuals with prodromal and clinical PD. It will be designed to impart knowledge (e.g. on sustainability and health effects) and food literacy (e.g. food merchandize and culinary skills) in group meetings and culinary medicine workshops. Recipe suggestions and shopping guides will consider individual abilities and needs and a web-application is used for information, increasing self-efficacy, motivation, and monitoring. To ensure an easy integration of the diet into everyday life, partners will be included in the program, if applicable. Moreover, cultural preferences as well as financial resources will be considered. Regular feedback using statistics on nutrient intake and overall progress will be implemented to encourage adherence.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anja Bosy-Westphal, PhD, MD; Phone Number: +494318805674; Email: abosyw@nutrition.uni-kiel.de
• Study Contact Backup: Name: Eva Schäffer, MD; Phone Number: +49431 500 23800; Email: eva.schaeffer@uksh.de

Study Locations

• Germany
  • Kiel, Germany, 24105
    • Institute of Human Nutrition
  • Kiel, Germany, 24105
    • Kiel University, University Hospital Schleswig-Holstein
    • Contact: Eva Schäffer, MD; Phone Number: +49431 500 23800; Email: eva.schaeffer@uksh.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients with probable prodromal PD (according to predefined criteria)
• patients with clinical PD with slight to moderate disease severity (Hoehn & Yahr 1-2.5)
• habitual Western Diet (≥30% of energy intake from ultra-processed food)

Exclusion Criteria:

• current adherence to a plant-based diet
• food allergies or intolerances
• significant diseases of the gastrointestinal system (e.g. celiac disease) or central nervous system, diabetes mellitus
• underweight (BMI <18.5 kg/m2)
• active smoking
• expected changes in medication or antibiotic treatment during the intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with prodromal PD on New Nordic LPF-diet (intervention); Patients with prodromal PD will take part in an 8-week patient-centered intervention program on a predominantly plant-based New Nordic LPF-Diet.	Behavioral: 8 week predominantly plant-based New Nordic LPF-diet program; An 8-week patient-centered dietary intervention program will be implemented to maintain a predominantly plant-based New Nordic LPF-Diet.; Behavioral: maintenance of the predominantly plant-based New Nordic LPF-diet; Follow-up of long-term adherence to the diet at one and six months after completion of the intervention program.
Experimental: Patients with clinical PD on New Nordic LPF-diet (intervention); Patients with clinical PD will take part in an 8-week patient-centered intervention program on a predominantly plant-based New Nordic LPF-Diet. Patients with clinical PD will be randomized to intervention or control group.	Behavioral: 8 week predominantly plant-based New Nordic LPF-diet program; An 8-week patient-centered dietary intervention program will be implemented to maintain a predominantly plant-based New Nordic LPF-Diet.; Behavioral: maintenance of the predominantly plant-based New Nordic LPF-diet; Follow-up of long-term adherence to the diet at one and six months after completion of the intervention program.
No Intervention: Patients with clinical PD receiving standard of care (control); Patients with clinical PD will receive standard of care information on a healthy diet and serve as control. Patients with clinical PD will be randomized to intervention or control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
abundance of key SCFA-producing gut bacteria	analysis of stool samples	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
systemic inflammation markers	hsCRP and IL-6 in serum	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
metabolic resilience	modeling of one parameter (metabolic resilience) including information on postprandial glucose, insulin, triglycerides and NEFA following a mixed meal tolerance test	pre vs. post intervention (8 weeks)
gastrointestinal peptide-hormones	ghrelin, GLP-1, PYY	pre vs. post intervention (8 weeks)
energy balance	changes in body weight	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
energy partitioning	changes in body composition	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical motor symptoms	clinical examination	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
clinical non-motor symptoms	clinical examination	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
gastric emptying	13C-breath test	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
gastrointestinal transit time	using a test meal with food colouring and the time to colour appearance in stool	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
gut motility	functional visceral MRI	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
dietary adherence via serum markers	serum carotinoid and Trimethylamine oxid-levels will be combined and tertiles will be formed	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
dietary adherence via healthy Nordic food Index	healthy Nordic food Index using data from a food frequency questionnaire	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
food literacy effectiveness	self-perceived food literacy scale (questionnaire)	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
patient acceptance	Parkinson's Disease Questionnaire (PDQ-39)	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
patient quality of life	Ways of Coping Questionnaire (WCQ)	pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention

Collaborators and Investigators

• Sponsor: University of Kiel
• Collaborators: University Hospital Schleswig-Holstein
• Investigators: Principal Investigator: Anja Bosy-Westphal, PhD, MD, Kiel University; Principal Investigator: Eva Schäffer, MD, Kiel University, University Hospital Schleswig-Holstein

Publications and helpful links

General Publications

• Aho VTE, Houser MC, Pereira PAB, Chang J, Rudi K, Paulin L, Hertzberg V, Auvinen P, Tansey MG, Scheperjans F. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease. Mol Neurodegener. 2021 Feb 8;16(1):6. doi: 10.1186/s13024-021-00427-6.
• Maraki MI, Yannakoulia M, Stamelou M, Stefanis L, Xiromerisiou G, Kosmidis MH, Dardiotis E, Hadjigeorgiou GM, Sakka P, Anastasiou CA, Simopoulou E, Scarmeas N. Mediterranean diet adherence is related to reduced probability of prodromal Parkinson's disease. Mov Disord. 2019 Jan;34(1):48-57. doi: 10.1002/mds.27489. Epub 2018 Oct 10.
• Solch RJ, Aigbogun JO, Voyiadjis AG, Talkington GM, Darensbourg RM, O'Connell S, Pickett KM, Perez SR, Maraganore DM. Mediterranean diet adherence, gut microbiota, and Alzheimer's or Parkinson's disease risk: A systematic review. J Neurol Sci. 2022 Mar 15;434:120166. doi: 10.1016/j.jns.2022.120166. Epub 2022 Jan 26.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 11, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Parkinson's Disease; New Nordic Diet; Microbiome-Immune-Brain axis
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: CRC1697-C04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No