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Updated: Sep 24, 2025
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
The metabolic potential of the paediatric-onset multiple sclerosis gut microbiome
Ali I Mirza1, Feng Zhu1, Natalie Knox2
1Department of Medicine (Neurology), The University of British Columbia, Vancouver, BC, Canada.
Insights
The gut microbiome
Area of Science:
- Microbiome research
- Metabolic pathways
- Paediatric neurology
Background:
- Multiple Sclerosis (MS) can manifest in childhood.
- The gut microbiome's role in paediatric MS is under-explored.
Purpose of the Study:
- To investigate the gut microbiome's metabolic functions in children with MS.
- To compare metabolic potential between paediatric MS patients and healthy controls.
Main Methods:
- Analysis of stool metagenome gene abundances in 17 paediatric MS patients and 20 controls.
- Estimation of microbial metabolite abundances, turnover scores, and carbohydrate-active enzyme (CAZyme) diversity.
- Comparison of MS patients and controls, and of disease-modifying drug (DMD)-exposed versus naïve MS patients.
Main Results:
- No significant difference in overall metabolite abundance between groups.
- Altered microbial metabolite turnover scores in MS patients, with higher potential for lipopolysaccharide metabolism but lower potential for peptidoglycan and starch metabolism.
- Underrepresentation of starch-degrading CAZyme subfamilies in MS patients, and in DMD-exposed versus DMD-naïve MS patients.
Conclusions:
- Paediatric-onset MS is associated with altered gut microbiome metabolic potential.
- MS patients exhibit increased lipopolysaccharide breakdown and decreased resistant starch metabolism.
- Gut microbiome alterations may be influenced by disease-modifying drug exposure in paediatric MS.
Background:
The aim of this study was to examine the gut microbiome's metabolic potential in paediatric-onset MS patients (symptom onset <18 years).
Methods:
We included 17 MS participants and 20 controls similar for sex, age, race, and stool consistency from the Canadian Paediatric Demyelinating Disease Network study. Stool-derived gut metagenome gene abundances were used to estimate relative abundances and turnover scores of individual microbial metabolites and the composition and diversity of carbohydrate-active enzymes (CAZymes). MS participants and controls were compared using the Wilcoxon rank-sum test, as were the disease-modifying drug (DMD) exposed and naïve MS participants.
Results:
The median age(s) at MS symptom onset=16.1 years (interquartile range [IQR]=1.7), and at stool sample procurement=16.9/15.8 years (IQR=2.0/1.4), for the MS participants/controls. Most MS and control participants were girls (80-82%). Five (29%) of the MS participants had never been exposed to a DMD pre-stool sample and 12 (71%) had (7 to beta-interferon and 5 glatiramer acetate). While the relative abundance of metabolites did not differ between MS participants and controls, turnover scores did. MS participants had a greater potential to metabolize lipopolysaccharides than controls (score difference=1.6E-04, p = 0.034) but lower potential to metabolize peptidoglycan molecules and starch (score differences<2.2E-02, p<0.040). Further, although CAZymes diversity did not differ (p>0.050), starch-degrading subfamilies were underrepresented in MS participants versus controls (relative abundance differences >-0.34, p<0.040) and in the DMD exposed verses DMD naïve MS participants (relative abundance differences>-0.20, p<0.049).
Conclusion:
Paediatric-onset MS participants had an altered gut microbiome-related metabolic potential compared to controls, including higher breakdown of lipopolysaccharide molecules, but lower resistant starch metabolism.
