Background/Purpose: Gastrointestinal involvement is recognized as a major cause of morbidity and mortality in systemic sclerosis (SSc). The pathophysiology is still unclear and includes impairment of motility, digestion, absorption and excretion. Few data on composition and function of gut micro-environment in SSc are reported in literature but there is a growing body of evidences supporting the hypothesis of a relation between gut microbiota, the host immune system and metabolic/nutritional status. The goal of this study was to characterize the gut microbiota in SSc patients compared to healthy subjects to investigate whether specific microbial species may be responsible of dysbiosis in SSc patients with gastrointestinal involvement. Furthermore, we investigated the composition of microbiota in different subsets of SSc according to patient’s nutritional status to verify if microbiota characteristics may be used as a biomarker for malnutrition and poor prognosis in patients with SSc.

Methods: A total of 66 SSc patients were enrolled: 66.7% presented a normal BMI, 15.1% were underweight, while 18.2% were overweight. Gastrointestinal involvement was evaluated through UCLA-GIT 2.0 questionnaire while nutritional status was assessed through the MUST and selected blood biomarkers (albumin, Vitamin D, Vitamin B12, folate, Ferritin, cholesterol). Faecal samples were obtained from SSc patients and healthy controls. The composition of microbiota was determined through 16S-rRNA pirosequencing performed using the GS Titanium technology (Roche 454). Dedicated statistic (LEfSe) was used to identify taxa that showed differential expression between the groups; α- and β-diversity and Firmicutes/Bacteroidetes ratio were determined.

Results: In our cohort of patients the mean total UCLA GIT 2.0 score was 0.4±0.3. The values representing species richness were significantly different in the SSc group compared to controls (p=0.009 for Shannon index mean values). Noticeably, this difference was mostly accountable to BMI>25 subgroup. Firmicutes/Bacteroidetes ratio was inverted (>1) in the SSc group compared to controls, as already reported in literature for obese patients. At genus level SSc patients showed a differential expression in 21 taxa compared to controls with higher levels of genera such as Ruminococcus, Roseburia, Lactobacillus and Faecalibacterium and a decrease of genera such as Clostridium, Odoribacter, Veillonella and Prevotella. The differences in microbiota composition between SSc patients and controls were supported also by principal coordinate analysis (PCoA) of the values representing phylogenetic distance of microbial communities between specimens. Conversely, there were no substantial differences among subgroups of SSc patients according to BMI and according with the any specific gastrointestinal tract symptoms reported in the questionnaires.

Conclusion: Our analysis demonstrates an altered and distinct composition of gut microbiota in SSc patients compared to healthy controls. This may be the result of the complex pathophysiology of the disease and, at the same time, it may perpetuate immunologic aberrations and contribute to its clinical features. Though in the overweight SSc patients there seems to exist an overlap with the distinctive microbiota of obese patients, no definitive data are available to explain the relation between the nutritional status and gut microbiota in SSc patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-intestinal-involvement-in-systemic-sclerosis-is-characterized-by-a-peculiar-gut-microbiota/