Related Experiment Video
Updated: Jul 11, 2025
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Short-chain fatty acid producers in the gut are associated with pediatric multiple sclerosis onset
Vinicius A Schoeps1, Xiaoyuan Zhou1, Mary K Horton2
1Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
Objective:
The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric-onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures.
Methods:
A multicenter case-control study in which 35 pediatric-onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self-reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co-occurrence networks and for predicting functional abundances based on marker gene sequences.
Results:
Two microbial co-occurrence networks (one reaching significance after adjustment for multiple comparisons; q < 0.2) were identified, suggesting interdependent bacterial taxa that exhibited association with disease status. Both networks indicated a potentially protective effect of higher relative abundance of bacteria observed in these clusters. Functional predictions from the significant network suggested a contribution of short-chain fatty acid producers through anaerobic fermentation pathways in healthy controls. Consistent family-level findings from an independent Canadian-US study (19 case/control pairs) included Ruminococaccaeae and Lachnospiraceae (p < 0.05). Macronutrient intake was not significantly different between cases and controls, minimizing the potential for dietary confounding.
Interpretation:
Our results suggest that short-chain fatty acid producers may be important contributors to multiple sclerosis onset.
Insights
Pediatric multiple sclerosis (MS) is linked to gut bacteria. This study found that certain bacteria, particularly short-chain fatty acid producers, may protect against MS onset in children.
Area of Science:
- Microbiome research
- Neuroimmunology
- Pediatric neurology
Background:
- The gut microbiome's role in multiple sclerosis (MS) is suggested by animal models, but human studies have yielded inconsistent results.
- Pediatric-onset MS offers a unique window to study the microbiome closer to disease onset, minimizing confounding factors like comorbidities and disease duration.
Purpose of the Study:
- To investigate the gut microbiome composition and function in pediatric-onset MS.
- To identify microbial associations with MS in children and understand potential protective mechanisms.
Main Methods:
- A multicenter, case-control study matched 35 pediatric MS cases with healthy controls.
- Utilized linear mixed effects models, weighted correlation network analyses, and PICRUSt2 for microbial and functional abundance predictions.
- Validated findings with an independent Canadian-US case/control cohort.
Main Results:
- Identified significant microbial co-occurrence networks associated with MS status.
- Observed a potentially protective effect of specific bacterial taxa, including Ruminococcaceae and Lachnospiraceae.
- Functional predictions indicated a role for short-chain fatty acid (SCFA) producers in healthy controls.
Conclusions:
- Gut microbiome alterations, specifically reduced SCFA-producing bacteria, may contribute to the onset of pediatric MS.
- SCFA-producing bacteria may play a protective role in the development of MS.
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