Research Report: Ternary Analysis of Mediterranean Diet, Gut Microbiota, and Juvenile Onset Multiple Sclerosis

Research Background

Multiple Sclerosis (MS) is an autoimmune disease in which the immune system attacks the protective layer of nerve cells. Numerous studies have indicated that environmental risk factors, such as low vitamin D levels and EB virus infection, are associated with MS. However, these factors alone are not sufficient to cause MS and may depend on other factors. Recently, there has been growing interest in the interaction between diet and gut microbiota, particularly in the context of MS, as these factors can exhibit immunomodulatory and neuroprotective effects. Specifically, the Mediterranean diet has been extensively shown to be associated with better health outcomes in the general population, including reduced mortality risk and lower risk of chronic diseases.

Research Source

This study, authored by Ali I. Mirza, Feng Zhu, et al., involves multiple institutions, including the University of British Columbia, Simon Fraser University, University of Toronto, and the University of California San Francisco. The study findings were published in the journal Communications Medicine, Volume 4, Issue 148, in 2024.

Research Methods

Study Design

The study used a case-control design and included 95 participants (44 juvenile onset MS cases and 51 healthy controls) from the Canadian Pediatric Demyelinating Disease Network. All participants completed a food frequency questionnaire before the age of 21, and 59 provided fecal samples.

Research Process

1. Participant Selection and Data Sources: Participants were recruited through seven sites of the Canadian Pediatric Demyelinating Disease Network (six Canadian sites and one U.S. site). All sites obtained ethics committee approval and ensured informed consent was signed by all participants and/or their parents or legal guardians.

2. Dietary Assessment: The Mediterranean Diet Score (AMED) was used, which is based on seven dietary components including fruits, vegetables, legumes, whole grains, fish, red and processed meats, and the ratio of monounsaturated to saturated fatty acids.

3. Microbiota Sampling and Processing: Fecal samples from participants were collected using provided sampling tools and stored at -80 °C. DNA was extracted from fecal samples and analyzed using 16S rRNA gene V4 region amplification and sequencing.

4. Statistical Analysis: Data analysis for diet groups and diet-microbiota subgroups included logistic regression, linear regression, and mediation analysis. Microbiota data was processed using centered log-ratio transformation to remove erroneous sequences.

Data and Results

1. Dietary-Related Results: Higher Mediterranean Diet Scores and higher intakes of fiber (grams per day), whole grains (equivalent ounces/day), and iron (milligrams per day) were associated with a reduced risk of MS. Each 1-point increase in the Mediterranean Diet Score decreased the risk of MS by 37%.

2. Diet-Microbiota Related Results: The Mediterranean Diet Score and fiber intake had significant effects on gut microbiota. Specifically, the abundance of certain bacterial groups, such as Methanobrevibacter, increased significantly in MS patients, while Clostridiales vadin bb60 group and Ruminococcaceae NK4A214 group decreased significantly in MS patients.

Research Conclusion and Significance

The study found that higher Mediterranean Diet Scores and higher nutrient intakes were associated with a reduced risk of juvenile onset multiple sclerosis. These nutrients may exert a protective effect by influencing the composition of the gut microbiota and regulating the host immune response. These findings highlight the critical importance of the host-microbiota-diet ternary relationship in MS.

Research Highlights

1. Protective Effect of Dietary Patterns on MS: The Mediterranean diet and its components demonstrated a significant protective effect in reducing the risk of MS.

2. Mediating Role of Gut Microbiota: Certain gut bacterial groups may mediate the protective role of the Mediterranean diet on MS.

3. Methodological Innovation: The study applied a ternary analysis method, systematically assessing the relationship between diet, gut microbiota, and juvenile MS for the first time.

4. Accurate Data Analysis: Multiple statistical methods, including logistic regression, linear regression, and mediation analysis, were used to ensure the precision and reliability of the results.

Other Important Information

1. Future Research Directions: Larger longitudinal studies are recommended to verify whether these diet-gut microbiota relationships are causal.

2. Study Limitations: The current study is cross-sectional and cannot determine causality. Additionally, the limited sample size may not capture all significant relationships.

This study provides valuable insights into the relationship between the Mediterranean diet, gut microbiota, and juvenile onset multiple sclerosis, and opens new avenues for exploring the potential protective role of diet in MS.