Gut microbiome of treatment-na\xefve MS patients of different ethnicities early in disease course

R E Ventura,T Iizumi,M J Blaser,T Battaglia,Menghan Liu,J Herbert,G I Perez-Perez

doi:10.1038/s41598-019-52894-z

R E Ventura, T Iizumi + Show 5 more

Open Access

https://doi.org/10.1038/s41598-019-52894-z

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Abstract

Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium, compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.

Highlights

Evidence has been emerging for a role of alterations in the gut microbiome in several autoimmune diseases including MS1–8, presumably through interactions between the intestinal microbiome and the host immune system
Differences in the microbiome could potentially lead to differences in disease severity, and given that the microbiome may segregate across ethnic populations[23,24], we sought to separately analyze the microbiota in members of three major ethnic groups in the populations we serve: African Americans (AA), Hispanics (HA), and Caucasians (CA)
We enrolled a total of 45 patients with Multiple Sclerosis (MS) from the following ethnic groups: Caucasian Americans [CA (15)], Hispanic Americans [HA (16)], and African Americans [AA (14)] (Table 1)

Summary

Introduction

Evidence has been emerging for a role of alterations in the gut microbiome in several autoimmune diseases including MS1–8, presumably through interactions between the intestinal microbiome and the host immune system. To capture any potential effect of the microbiome on MS disease initiation, it is ideal to examine early in the disease course and to avoid subjects that have received disease-modifying agents (DMTs), since disease drift over time[14], comorbid conditions such as constipation[15], and exposure to DMTs1,16,17 could affect microbiome composition. Differences in the microbiome could potentially lead to differences in disease severity, and given that the microbiome may segregate across ethnic populations[23,24], we sought to separately analyze the microbiota in members of three major ethnic groups in the populations we serve: African Americans (AA), Hispanics (HA), and Caucasians (CA). We evaluated the gut microbiota in subjects who were naïve to disease-modifying treatments, most of whom had newly diagnosed MS, in each of the three ethnic groups. Using two different analytical approaches, we identified a single taxon associated with MS cases across all three ethnic groups

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