Abstract
Within the last decade, numerous studies have demonstrated changes in the gut microbiome associated with specific autoimmune diseases. Due to differences in study design, data quality control, analysis and statistical methods, many results of these studies are inconsistent and incomparable. To better understand the relationship between the intestinal microbiome and autoimmunity, we have completed a comprehensive re-analysis of 42 studies focusing on the gut microbiome in 12 autoimmune diseases to identify a microbial signature predictive of multiple sclerosis (MS), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and general autoimmune disease using both 16S rRNA sequencing data and shotgun metagenomics data. To do this, we used four machine learning algorithms, random forest, eXtreme Gradient Boosting (XGBoost), ridge regression, and support vector machine with radial kernel and recursive feature elimination to rank disease predictive taxa comparing disease vs. healthy participants and pairwise comparisons of each disease. Comparing the performance of these models, we found the two tree-based methods, XGBoost and random forest, most capable of handling sparse multidimensional data, to consistently produce the best results. Through this modeling, we identified a number of taxa consistently identified as dysregulated in a general autoimmune disease model including Odoribacter, Lachnospiraceae Clostridium, and Mogibacteriaceae implicating all as potential factors connecting the gut microbiome to autoimmune response. Further, we computed pairwise comparison models to identify disease specific taxa signatures highlighting a role for Peptostreptococcaceae and Ruminococcaceae Gemmiger in IBD and Akkermansia, Butyricicoccus, and Mogibacteriaceae in MS. We then connected a subset of these taxa with potential metabolic alterations based on metagenomic/metabolomic correlation analysis, identifying 215 metabolites associated with autoimmunity-predictive taxa.
Highlights
The human intestine is colonized by millions of microbes, which have been shown to be involved in metabolism (Nicholson et al, 2012), immunity (Belkaid and Hand, 2014), and host physiology (Dominguez-Bello et al, 2019)
The NCBI PubMed database was searched for publications on April 1, 2020 related to the gut microbiome in autoimmune diseases from the last 10 years based on the following criteria: (1) the study was performed on human fecal samples; (2) the subjects in the studies were older than 2 years old; (3) the samples were sequenced with either 16S rRNA sequencing or shotgun metagenomics or both; (4) the raw data in FASTQ format were publicly available; (5) the provided metadata allowed us to distinguish between disease and healthy control samples, as well as between subjects who were explicitly treated in the study and untreated samples
We used data from 42 studies investigating the role of the human gut microbiome in autoimmune disease, assessing both general autoimmunity, and specific diseases
Summary
The human intestine is colonized by millions of microbes, which have been shown to be involved in metabolism (Nicholson et al, 2012), immunity (Belkaid and Hand, 2014), and host physiology (Dominguez-Bello et al, 2019). This complex ecosystem has been extensively studied in the context of disease (Gilbert et al, 2016; Duvallet et al, 2017), diet (Carmody et al, 2015; Singh et al, 2017; Ruggles et al, 2018), and age (O’Toole and Jeffery, 2015) with the goal of determining how specific taxa and, more recently, the gene expression patterns of these taxa, impact human health. The question of whether there are common microbial features characterizing general autoimmunity still remains
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