Experimental autoimmune encephalomyelitis is associated with changes of the microbiota composition in the gastrointestinal tract

David M Johanson,Jennifer E Goertz,Alban Gaultier,Ioana A Marin,John Costello,Christopher C Overall

doi:10.1038/s41598-020-72197-y

David M Johanson, Jennifer E Goertz + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-72197-y

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Abstract

The gut microbiome is known to be sensitive to changes in the immune system, especially during autoimmune diseases such as Multiple Sclerosis (MS). Our study examines the changes to the gut microbiome that occur during experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We collected fecal samples at key stages of EAE progression and quantified microbial abundances with 16S V3–V4 amplicon sequencing. Our analysis of the data suggests that the abundance of commensal Lactobacillaceae decreases during EAE while other commensal populations belonging to the Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae families expand. Community analysis with microbial co-occurrence networks points to these three expanding taxa as potential mediators of gut microbiome dysbiosis. We also employed PICRUSt2 to impute MetaCyc Enzyme Consortium (EC) pathway abundances from the original microbial abundance data. From this analysis, we found that a number of imputed EC pathways responsible for the production of immunomodulatory compounds appear to be enriched in mice undergoing EAE. Our analysis and interpretation of results provides a detailed picture of the changes to the gut microbiome that are occurring throughout the course of EAE disease progression and helps to evaluate EAE as a viable model for gut dysbiosis in MS patients.

Highlights

The gut microbiome is known to be sensitive to changes in the immune system, especially during autoimmune diseases such as Multiple Sclerosis (MS)
Our approach can be divided into three main arms: (1) Pairwise differential abundance analysis to reconstruct the changes in populations of individual bacterial taxa over time; (2) Construction of microbial co-occurrence networks to infer EAE-induced changes to microbe-microbe interactions and community structure from abundance data and; (3) Application of PICRUSt2 and weighted gene co-expression network analysis (WGCNA)[10] to impute metagenomic abundances and identify putative associations between MetaCyc Enzyme Consortium (EC)[11] pathways and disease parameters
EAE group mice presented with ascending paralysis and weight loss that are characteristic of EAE (Fig. 1A,B), while the Complete Freund’s Adjuvant (CFA) and naïve groups appeared normal

Summary

Introduction

The gut microbiome is known to be sensitive to changes in the immune system, especially during autoimmune diseases such as Multiple Sclerosis (MS). Our study examines the changes to the gut microbiome that occur during experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Upon transfer in a GF spontaneous model of EAE3 Taken together, these pieces of evidence support a strong link between MS and the microbiome and warrant further studies to fully understand how the microbiome influences disease initiation and progression. Our approach can be divided into three main arms: (1) Pairwise differential abundance analysis to reconstruct the changes in populations of individual bacterial taxa over time; (2) Construction of microbial co-occurrence networks to infer EAE-induced changes to microbe-microbe interactions and community structure from abundance data and; (3) Application of PICRUSt2 and weighted gene co-expression network analysis (WGCNA)[10] to impute metagenomic abundances and identify putative associations between MetaCyc Enzyme Consortium (EC)[11] pathways and disease parameters. Our findings have the potential to generate hypotheses that could lead the way toward the development of gut centric therapeutic avenues for MS patients

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