OP0213 Systemic Sclerosis is Associated with a Unique Colonic Microbial Consortium

Abstract

BackgroundGastrointestinal tract (GIT) dysfunction affects most patients with systemic sclerosis (SSc) and is a leading cause of morbidity. While the etiology of SSc-related lower GIT dysfunction remains elusive, evidence suggests that bacterial overgrowth is a feature of SSc. However, no studies have directly examined the colonic microbial consortium of SSc patients.ObjectivesTo compare colonic microbial composition of SSc patients and healthy controls. To determine whether microbial composition alterations are associated with lower GIT symptoms.MethodsAdults 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). At baseline, participants underwent a colonoscopy and cecum and sigmoid mucosal lavage samples were obtained. Patients also 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. Similarity between microbial communities in sample groups were determined by computing unweighted UniFrac distances between samples with QIIME. Principal coordinate analysis (PCoA) was performed to visualize the resulting UniFrac distance matrix. To identify differentially abundant bacterial phylotypes at the genus-taxonomy level, pairwise comparisons (Kruskal-Wallis test) between SSc and healthy samples were computed. Multiple hypothesis tests were adjusted by computing Benjamini and Hochberg false discovery rates (FDR) and a significant association was defined at the FDR q-value threshold below 0.05.Results17 patients with SSc (88% Female; Median age 52.1 years; Median disease duration 7.1 years) underwent colonoscopy. The mean (SD) GIT 2.0 scores were: Total: 0.7 (0.6); Distension/Bloating: 1.5 (0.9); Fecal soilage 0.5 (0.9); Diarrhea 0.4 (0.6); Social functioning 0.5 (0.5); Emotional Well-being 0.5 (0.7); Constipation 0.7 (0.7). PCoA illustrated significant differences in the microbial communities in SSc versus healthy controls in both the cecum (R2=0.9, p=0.001) and sigmoid (R2=0.9, p=0.002) (Figure 1). Pairwise comparisons between SSc and healthy samples demonstrated numerous significant differences in bacterial genera of the cecum and sigmoid. Similar to chronic inflammatory states, such as inflammatory bowel disease (IBD), SSc patients had decreased commensal genera, such as Bacteroides and Faecalibacterium, and increased pathogenic genera, such as Enterobacteriales and Fusobacterium, compared with healthy controls in the cecum and sigmoid. However, SSc patients had increased sigmoid and cecum Bifidobacterium, which is typically found in lower abundance in IBD. Additional taxa alterations were observed, and the relationship between the microbial consortium and GIT symptoms was also explored and will be presented.ConclusionsThis study...

Gastrointestinal involvement in systemic sclerosis: Effects on morbidity and mortality and new therapeutic approaches

“…26,27 The first study to explore the GI microbiome in SSc (n = 17) demonstrated that patients with SSc had an altered microbiota composition compared with healthy age- and gender-matched controls in an analysis of colonic lavage specimens. 28 We subsequently compared the microbiota of two independent SSc cohorts (UCLA and OUH, n = 34) and found similar alterations in GI microbiota of SSc patients compared with controls in an analysis of stool specimens. 29 Similar findings were also reported by in an Italian SSc cohort including 59 SSc patients.…”

“…26,27 The first study to explore the GI microbiome in SSc (n = 17) demonstrated that patients with SSc had an altered microbiota composition compared with healthy age-and gender-matched controls in an analysis of colonic lavage specimens. 28 We subsequently compared the microbiota of two independent SSc cohorts (UCLA and OUH, n = 34) and found similar alterations in GI microbiota of SSc patients compared with controls in an analysis of stool specimens.29 Similar findings were also reported by in an Italian SSc cohort including 59 SSc patients.30 Cross-sectional data from a relatively large Swedish SSc cohort (n = 98) provided further evidence of an association between GI microbiome alterations and GI symptoms.31 This study also found that fecal calprotectin levels were higher in SSc patients with GI dysbiosis compared with SSc patients without dysbiosis, suggesting that inflamma-tion may moderate the relationship between GI microbiota alterations and GI symptoms in SSc.31 These studies have demonstrated that specific bacterial genera and species are associated with improvement or worsening in GI symp-toms, suggesting that a possible strategy for alleviating GI symptoms in SSc could target selective augmentation or elimination of specific bacterial species.…”

Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases

“…Moreover, recent host genome–microbiome association studies revealed that these genes were among those associated with microbiome composition. According to a study conducted by Volkmann et al ., which considered the gut microbiota of 17 systemic sclerosis patients and an equal number of healthy controls in order to reveal potential pathobionts, the differentiation of the gut microbiota associated with the disease shows significant similarities with the gut dysbiosis of Crohn’s disease [ 13 ]. This observation implies that autoimmune diseases may share characteristic host-microbiome variations.…”

Paul Klee’s gastrointestinal maladies: A series of historical and clinical vignettes, part IV

“…In addition, studies directed to the nature and potential role of the gut microbiome present a new and exciting avenue of research that one day may lead to a better understanding of SSc pathogenesis. 2,17…”