Alterations of Gut Microbiome in Rheumatoid Arthritis

Abstract

Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Recent studies have indicated that the pathogenesis of RA requires the interaction between genetic and environmental factors, such as gut microbiome. However, current evidence for the alterations of gut microbiome in RA is still limited. Thus, our study aimed to analyze the fecal samples from a cohort patient with RA and to identify the associated alterations in gut microbiome when compared to healthy controls. Methods: Fecal samples were obtained from treatment-naïve RA patients (n=50) and healthy controls (n=50). High-quality 16S rDNA V3–V4 sequences were extracted from fecal samples and further sequenced on a 454 Genome Sequencer platform for bioinformatics analysis, resulting in operational taxonomic units (OTUs) related to gut microbiota and phylogenetic tree. Clinical parameters of RA were correlated with specific microbial taxa by Correlation analysis. Results: A total of 121227 OTUs was clustered at 97 % sequence similarity and assigned taxonomic lineages by comparison with the Ribosomal Database Project database. The OTUs were classified into 35 phylums, 73 classes, 143 orders, 280 families, and 1165 genus. Intriguingly, our data revealed a lower alpha diversity, including richness, evenness and Shannon Index, as well as a lower Firmicutes / Bacteroidetes ratio in the gut microbiome of RA patients when compared with the healthy controls (Figure 1a, b). Moreover, at genus level, our taxonomic analysis identified 288 differentially abundant taxa (P< 0.05) (Figure 2a), among which 6 taxa, including Bacteroides, Parabacteroides, Paraprevotella, Porphyromonadaceae, Phascolarctobacterium and Carnobacterium, were significantly enriched in the gut microbiome of RA patients (Figure 2b, c). Conversely, a series of butyrate-producing taxa such as Faecalibacterium, Roseburia, Subdoligranulum, Ruminococcus and Pseudobutyrivibrio were depleted in RA patients but enriched in healthy controls (Figure 2b, c). Furthermore, we found a negative correlation (P<0.05) between the abundance of butyrate-producing Roseburia and the clinical parameters of disease status and activity such as erythrocyte sedimentation rate and the blood level of rheumatoid factors (IgM) (Figure 3). Conclusions: In the present study, we demonstrated that the composition of the gut microbiome in RA patients differed from that in healthy individuals. Our results revealed a decreased microbial diversity accompanied by altered microbial abundance in the gut microbiome of RA patients, which could be characterized as ‘dysbiosis’ and associated with the disease status and activity. The identified alterations in the gut microbiome might provide an updated overview for postulating molecular understandings and therapeutic strategy in RA.Figure 2. Differentially abundant gut microbiome in RA patients. (a) Data of phylogenetic tree analysis to identify differentially abundant taxa. (b) Percentage of 16S reads of major genus of the gut microbiota of RA patients and controls. (c) Quantification of differentially abundant genus of gut microbiome in RA and Control groups.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3. Abundance of Roseburia negatively correlated with the clinical parameters of disease activity in RA patients. Upper pannel: Correlation analysis of the 16S reads number of Roseburia and the erythrocyte sedimentation rate (ESR) in RA patients. Lower pannel: Correlation analysis of the 16S reads number of Roseburia and the blood level of rheumatoid factors (IgM) in RA patients. Note: Pearson rank correlation test was performed to determine correlations in the study variables.View Large Image Figure ViewerDownload Hi-res image Download (PPT)