Gut microbiota species correlates with relapse risk in pediatric MS

A “high relative abundance” of a gut microbiota species in the Blautia genus correlated with a greater risk for MS relapse in pediatric patients, according to findings presented during an encore session of MSVirtual2020.

The study represents the largest of its kind in MS, but the findings need to be replicated in larger investigations, the researchers noted.

“What we do know about the gut microbiome in MS is largely from adult-onset cohorts,” Mary Horton, MPH, epidemiology PhD candidate at University of California, Berkeley, said during her presentation. “The objective of this study was to identify whether there are features of the gut microbiome that are associated with relapse.”

The researchers obtained stool samples from pediatric cases of MS (symptom onset, < 18 years). They recruited patients from University of California, San Francisco, and six other centers within the U.S. network of pediatric MS centers between 2014 and 2018.

Horton and colleagues identified amplicon sequence variants (ASVs) with the Divisive Amplicon Denoising Algorithm-2 and removed ASVs not found in at least 20% of the sample. They used weighted genetic correlation network analysis (WGCNA) and sparse correlations for compositional data (sparCC) transformation of ASV abundance to group ASVs into modules. The researchers also used Cox proportional hazard recurrent event models for an adjusted analysis of the link between individual ASVs and ASV clusters, accounting for age, sex and use of disease-modifying treatment.

The mean follow-up time was 2.5 years. During this period, 91% of the cohort used a disease-modifying treatment.

Data from 53 pediatric stool samples (girls: 72%; mean age: 15.5 years; mean disease duration: 1.1 years) identified 270 ASVs for further analysis. Fewer than half of patients (45%) experienced one relapse; 30% had more than one relapse during follow-up.

Of the 270 ASVs analyzed, 20 were nominally significant (P < .05). The presence of Blautia stercoris correlated with higher relapse risk (HR = 2.50; 95% CI, 1.43-4.37).

WGCNA identified 6 ASV modules. Higher values of one module’s eigengene correlated with greater relapse risk (HR = 1.23; 95% CI, 1.02-1.50). This module included four ASVs that were nominally linked to a higher risk for relapse, including Blautia massiliensis, Dorea longicatena, Coprococcus comes and a species of the genus Subdoligranulum that researchers described as “unknown.”

“There are not broad differences in gut bacterial composition that are associated with relapse. However, we did determine that members of the Blautia genus are associated with relapse, as well as their neighbors with the cluster,” Horton said. “This is the largest MS dataset, whether it is adult or pediatric patients, that has both microbiome and relapse data. However, it is still a relatively small sample. This work needs to be followed up on in order to confirm the findings.”