Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts

Abstract

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5–16.4) and 7.0 (1.0–19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state.

Microbial and metabolic multi‐omic correlations in systemic sclerosis patients

“…Here, microbial genera and species elsewhere related to inflammatory bowel disease (IBD) were found to be associated with the severity of GIT symptoms. Similar results were found in stool sample analysis when comparing the same patients with 17 patients from Norway . Recent work on 18 Italian SSc patients showed specific microbial differences between SSc patients with or without gastroenteric involvement .…”

“…Differences in gut microbiota were indeed observed in SSc when the same U.S. population described in Ref. was compared to a similar sample of Norwegian patients . Another source of variability with respect to the study by Volkmann et al .…”

“…Despite these considerations, and regardless of the specific findings, our results are in full accordance with other studies (see Refs. and ), suggesting the presence of a proinflammatory microbial flora in SSc patients, which may have functional consequences on the intestinal integrity.…”

“…Several studies focusing on microbiota in autoimmune diseases have found distinct profiles in patients with systemic lupus erythematosus (SLE), inflammatory arthritis, and spondyloarthritis . A few studies conducted in relatively small case‐series have studied microbiota in SSc . A first study found a distinct colonic microbial signature on cecum and sigmoid mucosal lavage samples in 17 SSc patients compared with healthy controls (HCs) .…”

“…13,14 A few studies conducted in relatively small case-series have studied microbiota in SSc. [15][16][17] A first study found a distinct colonic microbial signature on cecum and sigmoid mucosal lavage samples in 17 SSc patients compared with healthy controls (HCs). 16 Here, microbial genera and species elsewhere related to inflammatory bowel disease (IBD) were found to be associated with the severity of GIT symptoms.…”