Background/Purpose: Gastrointestinal
tract (GIT)
dysfunction is a leading cause of morbidity in patients with systemic sclerosis
(SSc). However, the
etiology of SSc-related lower GIT dysfunction remains
elusive. The purpose of the present study was to compare colonic microbial composition of SSc patients and healthy controls and to determine whether
certain microbial genera are associated with SSc-GIT
symptoms.

Methods: Adults
SSc patients who had no contraindication to
colonoscopy were eligible to participate. Patients were excluded if they were
on chronic antibiotic therapy. Healthy controls were age- and gender-matched to SSc
patients (1:1). Cecum and sigmoid mucosal lavage samples were obtained during
colonoscopy. SSc patients completed the GIT 2.0
questionnaire to assess GIT symptom
severity at the time of colonoscopy.
The microbiota from these samples were determined by Illumina HiSeq 2000 16S
sequencing, and operational taxonomic units (OTU) were selected using the Greengenes database at 97% identity. Linear Discriminant
Analysis (LDA) Effect Size was used to identify the genera that showed
differential expression in SSc versus controls.
Multivariate Association with Linear Models (MaAsLn)
was used to identify specific genera associated with GIT symptoms.

Results: Among 17
patients with SSc (88% Female; Median age 52.1
years), the mean (SD) total GIT 2.0 score was 0.7 (0.6). Principal coordinate
analysis illustrated significant microbial community differences in SSc versus healthy controls in the cecum (p=0.001) and
sigmoid (p=0.001) regions (Figure 1). Similar to inflammatory disease states, SSc patients had decreased commensal genera, such as Faecalibacterium
and Clostridium and increased
pathogenic genera, such as Fusobacterium, Erwinia and Trabsulsiella compared with healthy controls. However, SSc patients had increased Bifidobacterium and Lactobacillus, which are typically
reduced in inflammation. Increased Erwinia and Trabsulsiella levels were associated with increased scores
on the constipation and diarrhea domains of the GIT 2.0.

Conclusion: This study
demonstrates a distinct colonic microbial signature in SSc
patients compared with healthy controls. This unique ecological change may
perpetuate immunological aberrations and contribute to clinical manifestations
of SSc.

Figure 1.
Significant differences in the beta diversity of the SSc
and healthy samples as demonstrated by principal coordinate analysis plots of
the unweighted UniFrac
distance for the cecum (top panel) and sigmoid (bottom panel) samples. Each dot
represents a sample from a SSc patient (closed
circle) or a healthy control (open circle).