SAT0090 GUT MICROBIOTA COMPOSITION IS CONTINGENT WITH DISEASE PHASES IN RHEUMATOID ARTHRITIS
Authors: Elisa Gremese, Francesco Cianci, Stefano Alivernini, Giulia Menchinelli, Anna Laura Fedele, Barbara Tolusso, Brunella Posteraro, Maurizio Sanguinetti
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Increasing evidences suggest that alterations in the gut microbiota may contribute to the pathogenesis and influence the clinical outcome of Rheumatoid arthritis (RA). <h3>Objectives:</h3> To characterize the gut microbiota composition in RA patients in different disease phases contingently to therapeutic regimens. <h3>Methods:</h3> Forty-four RA patients (7 naïve to treatment, 13 MTX-IR and 24 in sustained clinical and ultrasound remission under conventional and bDMARD combination therapy, respectively) (age 55.2±11.4 years, 79.5% female and 59.1% positive for ACPA and/or RF) and 20 age/sex matched healthy controls (HC) were enrolled in the study. At study entry, RA specific data set were collected and dietary habits were recorded using the 14-items Mediterranean Diet Adherence Screener (MeDAS) questionnaire. DNA was extracted from stool samples of each patient, amplified and 16S rRNA gene V3–V4 region was sequenced using an Illumina MiSeq<sup>TM</sup> platform. For downstream sequence analysis, a combination of software packages QIIME (v1.9.1) and VSEARCH (v1.1) was used and a biological observation matrix (BIOM) at different taxonomic levels (from phylum to genus) was produced. The BIOM was analysed using the Web-based program MicrobiomeAnalyst. Statistical analyses were performed using the R phyloseq software package. Differences in the relative abundance of individual bacterial taxa between a priori defined groups were assessed by LEfSe analysis. <h3>Results:</h3> Microbiota composition analysis showed that RA patients had a decrease in the gut microbial species richness compared to HC (p&lt;0.01). In particular, the principal coordinate analysis (PCoa) visualization of UniFrac distances and analysis of group similarities (ANOSIM) showed that faecal microbiota composition differs between RA and HC (p&lt;0.01) confirmed by the LEfSe analysis showing that RA microbiota is enriched of <i>Bacteroidetes</i> and <i>Proteobacteria</i>, whereas HC were enriched of <i>Verrucomicrobia</i> and <i>Firmicutes</i>. Considering the RA cohort, no significant differences in microbiota composition were found stratifying patients based on autoantibody profile, disease duration and BMI category. However, considering the disease phase, RA patients with active disease (DAS&gt;3.7) showed significant differences in α-diversity compared to RA patients in LDA or in sustained clinical and ultrasound remission (p=0.01) with a relative abundance of <i>Haemophilus parainfluenzae</i> in high disease activity patients (<i>p&lt;</i><i>0.01</i>). A slightly higher α-diversity in RA patients with the highest adherence to Mediterranean diet (p=0.10). <h3>Conclusion:</h3> Despite limited sample size, this study strengthen the concept of significant microbiota differences in RA, contingently with disease phases, compared to HC. The evaluation of microbiota composition in the patients follow-up according to response to therapies is ongoing. <h3>Disclosure of Interests:</h3> Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Francesco Cianci: None declared, Stefano Alivernini Speakers bureau: BMS, Giulia Menchinelli: None declared, Anna Laura Fedele: None declared, Barbara Tolusso: None declared, Brunella Posteraro: None declared, Maurizio Sanguinetti: None declared