Gut microbiota composition and relapse risk in pediatric MS: A pilot study

Abstract

We explored the association between baseline gut microbiota (16S rRNA biomarker sequencing of stool samples) in 17 relapsing-remitting pediatric MS cases and risk of relapse over a mean 19.8 months follow-up. From the Kaplan-Meier curve, 25% relapsed within an estimated 166 days from baseline. A shorter time to relapse was associated with Fusobacteria depletion (p=0.001 log-rank test), expansion of the Firmicutes (p=0.003), and presence of the Archaea Euryarchaeota (p=0.037). After covariate adjustments for age and immunomodulatory drug exposure, only absence (vs. presence) of Fusobacteria was associated with relapse risk (hazard ratio=3.2 (95% CI: 1.2-9.0), p=0.024). Further investigation is warranted. Findings could offer new targets to alter the MS disease course.

Keywords: 16S rRNA; Cox regression; Gut microbiota; Kaplan-Meier; Pediatric multiple sclerosis; Relapse risk; Survival analyses.

Figure 1. Association between gut microbiota (phylum-level) and relapse for: Fusobacteria [panel A, top], Firmicutes [panel B: middle] and Euryarchaeota [panel C, bottom]

Panel A: Fusobacteria: Kaplan-Meier curves (left), absent (dashed line) vs. present (solid line). p=0.001, log-rank test. Panel B: Firmicutes: Kaplan-Meier curves (left), lower relative abundance (dashed line) vs. higher (solid line), p=0.003. log-rank test. Panel C Euryarchaeota: Kaplan-Meier curves (left), absent (dashed) vs present (solid linegreen), p=0.037, log-rank test. Key: IMD=immunomodulatory drug. Hazard ratios indicate risk of relapse from baseline and are derived from Cox regression hazards models. Age at baseline (stool collection) and IMD exposure at baseline (exposed vs. naïve) were used to adjust models as shown. Bold indicates p<0.05. Binomial categories for each phylum were created based on the data distribution as either absent versus present or high versus low (≤ vs. > median relative abundance). Of the Fusobacterium phyla identified, the genera were either Fusobacterium or Leptotrichia (genus was the lowest taxonomic level available).

Figure 1. Association between gut microbiota (phylum-level) and relapse for: Fusobacteria [panel A, top], Firmicutes [panel B: middle] and Euryarchaeota [panel C, bottom]

Panel A: Fusobacteria: Kaplan-Meier curves (left), absent (dashed line) vs. present (solid line). p=0.001, log-rank test. Panel B: Firmicutes: Kaplan-Meier curves (left), lower relative abundance (dashed line) vs. higher (solid line), p=0.003. log-rank test. Panel C Euryarchaeota: Kaplan-Meier curves (left), absent (dashed) vs present (solid linegreen), p=0.037, log-rank test. Key: IMD=immunomodulatory drug. Hazard ratios indicate risk of relapse from baseline and are derived from Cox regression hazards models. Age at baseline (stool collection) and IMD exposure at baseline (exposed vs. naïve) were used to adjust models as shown. Bold indicates p<0.05. Binomial categories for each phylum were created based on the data distribution as either absent versus present or high versus low (≤ vs. > median relative abundance). Of the Fusobacterium phyla identified, the genera were either Fusobacterium or Leptotrichia (genus was the lowest taxonomic level available).

Figure 1. Association between gut microbiota (phylum-level) and relapse for: Fusobacteria [panel A, top], Firmicutes [panel B: middle] and Euryarchaeota [panel C, bottom]

Panel A: Fusobacteria: Kaplan-Meier curves (left), absent (dashed line) vs. present (solid line). p=0.001, log-rank test. Panel B: Firmicutes: Kaplan-Meier curves (left), lower relative abundance (dashed line) vs. higher (solid line), p=0.003. log-rank test. Panel C Euryarchaeota: Kaplan-Meier curves (left), absent (dashed) vs present (solid linegreen), p=0.037, log-rank test. Key: IMD=immunomodulatory drug. Hazard ratios indicate risk of relapse from baseline and are derived from Cox regression hazards models. Age at baseline (stool collection) and IMD exposure at baseline (exposed vs. naïve) were used to adjust models as shown. Bold indicates p<0.05. Binomial categories for each phylum were created based on the data distribution as either absent versus present or high versus low (≤ vs. > median relative abundance). Of the Fusobacterium phyla identified, the genera were either Fusobacterium or Leptotrichia (genus was the lowest taxonomic level available).