Background/Purpose: A single center study demonstrated that systemic sclerosis (SSc) patients have a distinct colonic microbial consortium (based on lavage specimens) compared with healthy controls and that these ecological changes are associated with SSc-gastrointestinal tract (GIT) symptoms.¹ The purpose of the present study was to compare the fecal microbial composition in SSc patients from 2 independent cohorts and to determine whether certain microbial genera are associated with SSc-GIT symptoms.

Methods: Adults SSc patients from UCLA and Oslo University Hospital were eligible to participate. Healthy controls were also recruited (1:1). SSc patients completed the GIT 2.0 questionnaire to assess GIT symptom severity at the time of the stool collection. The microbiota from these samples were determined by Illumina HiSeq 2500 16S rRNA sequencing at UCLA, and operational taxonomic units were selected using the Greengenes database at 97% identity. Linear discriminant analysis effect size was used to identify the genera that showed differential expression in the two cohorts. Differential expression analysis for sequence count data was used to identify specific genera associated with GIT symptoms.

Results: 17 UCLA SSc patients (88% Female; Median age 52.1 years), 17 Oslo SSc patients (71% Female; Median age 60.5 years), and 17 healthy controls (60% Female; Median age 29.0 years) were enrolled. The mean (SD) total GIT 2.0 score was 0.7 (0.6) and 0.6 (0.5), and the median (IR) disease duration was 6.6 (2.5, 16.4) and 7.0 (1.0, 19.2) for the UCLA and Oslo cohorts, respectively. Principal coordinate analysis illustrated significant microbial community differences between the UCLA SSc and control cohorts (p=0.001) and between the Oslo SSc and control cohorts (p=0.002). At the genus level, SSc patients had significantly lower levels of protective commensal genera, such as Bacteroides (UCLA and Oslo), Faecalibacterium (UCLA), Clostridium (Oslo); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls (Figure 1). SSc patients with none/mild GIT symptoms had higher levels of commensal genera, such as Clostridium, compared with patients with moderate/severe GIT symptoms.

Conclusion: Consistent with the results of our prior study¹, the present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from two geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state. References: ¹Volkmann et al. Arthritis Rheum 2016;68:1483-92.     Figure 1. Genus level taxa associated with UCLA SSc patients versus healthy controls. Linear Discriminant Analysis (LDA) was used to calculate the effect size for these associations. Positive and negative effect sizes denote genera increased (red) or decreased (green) in SSc patients, respectively.