OP0085 Longitudinal analysis of the gastrointestinal microbiota in systemic sclerosis
Authors: ER Volkmann, A-M Hoffmann-Vold, Y-L Chang, J Jacobs, K Tillisch, E Mayer, PJ Clements, J Hov, M Kummen, Ø Midtvedt, V Lagishetty, Ø Molberg, J Braun
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gastrointestinal tract (GIT) dysfunction affects the majority of patients with systemic sclerosis (SSc). While the etiology of SSc-related lower GIT dysfunction remains elusive, we have recently demonstrated that the SSc disease state is associated with a distinct colonic microbial consortium and that specific genera are associated with SSc-GIT symptoms in a cross-sectional analysis using colonic lavage specimens.<sup>1</sup> <h3>Objectives</h3> To evaluate changes in GIT microbial composition over time in relation to GIT symptoms in SSc patients. <h3>Methods</h3> Adults SSc patients not on chronic antibiotic therapy were eligible to participate. Stool specimens were collected at 0, 3, 6, 9, and 12 months. Healthy controls were matched to SSc patients in a 1:1 ratio at baseline. SSc patients completed the GIT 2.0 questionnaire to assess GIT symptom severity at each collection time. The microbiota from these samples were determined by Illumina HiSeq 2500 16S sequencing. Linear Discriminant Analysis Effect Size was used to identify the genera that showed differential expression in SSc versus controls. Mixed models evaluated changes in GIT symptoms and microbial composition over time. <h3>Results</h3> Among 17 patients with SSc (88% Female; Median age 52.1 years), the mean (SD) baseline total GIT 2.0 score was 0.7 (0.6). The majority of participants (71%) provided at least 4 stool samples over the course of the 12-month study. Principal coordinate analysis illustrated significant microbial community differences in SSc versus healthy controls (p=0.001). Consistent with the results of our prior study using colonic lavage specimens,<sup>1</sup> SSc patients had decreased commensal genera, such as <i>Faecalibacterium</i> and <i>Bacteroides</i> and increased pathobiont genera, such as <i>Fusobacterium</i> and <i>Erwinia</i> compared with healthy controls (Figure 1). GIT 2.0 scores did not change significantly over the course of the 12-month study for each subject. However, patients with longer disease durations had increased GIT symptoms over time for the total score (P=0.0038), and the following domains: fecal soilage (P=0.0217), social functioning (P=0.0116), emotional well-being (P=0.0474), and constipation (P=0.0039). There was no difference in the course of GIT symptoms over time between patients with limited versus diffuse cutaneous disease. Both the absolute and relative abundances of specific genera did not change over time within individual subjects. After controlling for age, gender, ethnicity, disease duration and SSc subtype (i.e. limited vs. diffuse), low abundance of <i>Bacteroides</i> was associated with increased GIT symptoms over time. <h3>Figure 1. Genus level taxa associated with UCLA-SSc patients versus healthy subjects</h3> Negative and positive effect sizes denote genera decreased (blue) or increased (red) in SSc patients, respectively. <h3>Conclusions</h3> This study is the first to characterize lower GIT microbiota in SSc patients at multiple time points. The findings provide further evidence that lower GIT dysbiosis is a feature of the SSc disease state and that specific genera may contribute to GIT symptoms and serve as potential targets for therapeutic intervention. <h3>References</h3> Volkmann et al. Arthritis Rheumatol 2016;68:1483. <h3>Disclosure of Interest</h3> None declared