Methionine Intake Microbiota

Shaping Gut Microbiota Through a Dietary Intervention to Regulate Inflammatory Processes

Pro-inflammatory immune cells play a pivotal role in multiple sclerosis, and the gut microbiota is increasingly recognized as a key factor shaping the immune system. This study aims to determine the impact of a dietary intervention (methionine-restricted diet-MR) on gut microbiota and inflammation in humans. A randomized interventional pilot study with cross-over intervention is conducted in 40 healthy participants. For all participants, the first two weeks (week 1+week 2) consist of baseline assessment on their usual diet, and week 3+week 4 consist of MR diet only. For group A, the week 5+week 6 are MR+1,500 mg daily supplementation of methionine and for group B are MR+placebo, with a cross-over for week 7+week 8. Usual diet is resumed for all participants during week 9+week 10. Gut microbiota, blood levels of methionine and its metabolites, as well as immune and inflammatory markers will be evaluated every 2 weeks. It is hypothesized that MR could be used in humans to prevent and alleviate the course of multiple sclerosis by shaping the gut microbiota towards an anti-inflammatory profile, and that the gut microbiota is a biomarker associated with successful dietary interventions targeting inflammation in multiple sclerosis.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Behavioral: Methionine-restricted diet

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine Larochelle, MD, PhD; Phone Number: 15370 514 890-8000; Email: catherine.larochelle.med@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Recruiting
      • Centre de recherche du Centre Hospitalier de l'Universite de Montreal
      • Sub-Investigator: Bertrand Routy, MD, PhD
      • Contact: Catherine Larochelle, MD, PhD; Phone Number: 15370 514 890-8000; Email: catherine.larochelle.med@ssss.gouv.qc.ca
      • Principal Investigator: Catherine Larochelle, MD, PhD
      • Sub-Investigator: Chantal Bémeur, RD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adults
• 20-50 years old
• On omnivorous/western diet
• Understanding French or English

Exclusion Criteria:

• B12 deficiency
• Glomerular filtration rate <75 ml/h
• Liver dysfunction
• Pregnant or lactating
• Active inflammatory or infectious disease
• Insulino-dependent diabetes
• Active cancer
• Eating disorder
• BMI < 18.5 kg/m2
• Severe food allergies or intestinal problems or active substance dependence that would prevent adherence to the experimental diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methionine supplementation; Methionine supplementation will be achieved using commercially available methionine supplement (content methionine 500 mg, trice daily) with a monography from Health Canada (NPN 80017685) and compared to placebo pills.	Behavioral: Methionine-restricted diet; Methionine-restricted diet (plant-based diet) is a feasible and palatable way to achieve 50% reduction in methionine intake. Reduction to around 800 mg/day methionine will be achieved using participants' selection from low-methionine plant-based and ready to eat meals for 100% of their meals, for 6 weeks. Participants will be provided with education and a list of low methionine content food (green) and high methionine (red) for eating out, snacks and homemade meals.
Placebo Comparator: Placebo; Consumption of placebo pill trice daily for 2 weeks	Behavioral: Methionine-restricted diet; Methionine-restricted diet (plant-based diet) is a feasible and palatable way to achieve 50% reduction in methionine intake. Reduction to around 800 mg/day methionine will be achieved using participants' selection from low-methionine plant-based and ready to eat meals for 100% of their meals, for 6 weeks. Participants will be provided with education and a list of low methionine content food (green) and high methionine (red) for eating out, snacks and homemade meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota	Lipocalin-2 will be measured in stools to assess for inflammation in the gut. Stool samples from a given participant (all timepoints) will be processed simultaneously for DNA extraction and sequencing. Amplification of hyper-variable regions V1-V3 of 16S with primers, 16S libraries preparation and sequencing (Génome Québec) will be performed. Microbiota diversity will be measured with Shannon and α-diversity indexes. To represent microbial communities' similarity/difference between groups, a principal coordinates analysis (PCoA) will be used. Data will be interpreted by using high dimensional class comparisons via linear discriminant analysis of effect size (LEfSe) and volcano plots to identify potential relationships between specific bacteria and immunological/metabolomics results and clinical data.	At the end of week 2, 4, 6, 8, 10.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune and inflammatory profile	Established FACS panels will be used to characterize the complete immune profile including markers for B cells, T cells, myeloid cells, and CAMs implicated in gut and CNS homing. Validated multiplex immunoassays will be used on serum and supernatants to assess immune/inflammatory markers and metabolic markers (leptin, adiponectin, FGF21) in serum. In addition, sCD14, intestinal-type fatty acid-binding protein, and soluble suppression of tumorigenicity 2, which all correlated with gut damage in humans, will be measured.	At the end of week 2 ,4, 6, 8, 10.
Methionine level	Levels of methionine and its metabolites (SAM and SAH) will be measured by LC-MS (serum and PBMCs).	At the end of week 2, 4, 6, 8, 10.

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Multiple Sclerosis Society of Canada

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Estimated): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: inflammation; gut microbiota; methionine; diet intervention
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Inflammation
• Other Study ID Numbers: 23.111

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