Background/Purpose: Systemic sclerosis (SSc) is characterized by peripheral vasculopathy and widespread fibrosis of skin and internal organs. Up to 90% of SSc patients report gastrointestinal (GI) symptoms of varying severity. Small intestinal bacterial overgrowth by quantitative cultures and breath testing have been well described in SSc. However, no studies to date have assessed small intestinal microbial composition in SSc. We aimed to characterize the small bowel microbiome composition and in vivo intestinal absorption in SSc patients with and without GI symptom burden.

Methods: SSc patients meeting ACR/EULAR 2013 criteria were prospectively recruited. The UCLA GIT 2.0 questionnaire was used to evaluate GI symptom severity. Non-SSc healthy volunteers (HV) without any GI symptoms matched for age, sex and BMI were used as controls. Upper endoscopies were performed on SSc and healthy volunteers to collect duodenal aspirates, from which DNA was extracted and underwent 16S sequencing. Reads were processed via nf-core AmpliSeq pipeline (v.2.12) and Silva (v138) database for taxonomy assignment. Alpha diversity was calculated using R phyloseq package with beta diversity measured using the R GUniFrac and tested via PERMANOVA. Lactulose and 13C mannitol tracer-based testing was used to evaluate small intestinal (SI) permeability and absorptive capacity, respectively.

Results: 94 SSc participants (79 females; mean age ± SD: 58.0 ± 12.2 years) were enrolled, and a subset of these underwent SI microbiome analysis (n=28) and permeability testing (n=26). The average UCLA GIT 2.0 score for SSc participants was 0.6±0.4, indicating moderate GI disease severity. Compared to healthy volunteers (n=38), there is decrease in α-diversity in SSc (Observed, FDR< 0.001) suggesting decreased species richness and evenness as well as compositional changes in the microbiota structure as described by β-diversity measures (UniFrac FDR< 0.001). On taxonomic analysis, these differences were observed at all phylogenetic levels. Twelve differentially abundant bacterial species were identified (FDR< 0.01), with 9 in greater abundance in SSc patients. Of note, two species of Fusobacterium were in greater abundance in SSc, a genus previously identified to correlate with severity of GI symptoms in SSc. Firmicutes, which constitute a major phylum of the duodenal microbiome of healthy populations by providing a homeostatic role and aiding in absorption, were decreased in SSc individuals. SSc participants, compared to HV (n=29), had a lower cumulative 0–2-hour 13C mannitol excretion (6.7±4.6 vs 11.4±3.3 mg, P < 0.001), suggestive of decreased SI absorptive function.

Conclusion: This is the first and only study to our knowledge that has explored the SI microbiome composition in SSc. Impaired SI absorptive capacity coupled with a loss of microbiota diversity was observed in SSc patients. Expansion of pathobionts like Fusobacterium and depletion of Firmicutes colonizing the SI may contribute to fibrosis and worse GI function. Future work investigating the mechanisms of SI absorptive properties and the specific role of intestinal microbiota will be critical in addressing GI dysfunction in SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/small-bowel-microbial-dysbiosis-and-impaired-intestinal-absorptive-function-in-systemic-sclerosis-a-single-center-prospective-study/