The role of microbiota in different disease stages of systemic sclerosis: a possible impact in gastrointestinal tract disease activity?

Background Gastrointestinal tract (GIT) is affected in approximately 90% of systemic sclerosis (SSc) patients from the earliest disease stages. Microbiota has recently emerged as an important environmental factor in SSc pathogenesis. Objectives to test differences in the taxa composition of the fecal microbiota of very early SSc (VEDOSS) and established SSc patients. Methods Twenty-nine SSc patients classified according to the ACR/EULAR 2013 criteria (27 female, mean ± SD disease duration 13.1±9.2 years) and 21 VEDOSS patients (19 female, mean ± SD disease duration 6.4±5.2 years) were consecutively enrolled. For each patient, demographic, clinical and laboratoristic data were recorded and stool samples were collected. GI involvement and quality of life were investigated with UCLA-Gastrointestinal Tract Questionnaire (GIT)2.0 and Short Form Health Survey-36 (SF36). Microbiota was assessed through 16S rRNA Next Generation Gene-Sequencing analysis. Results We found a different fecal microbiota profile between SSc and VEDOSS. In particular, classes of Bacilli and Choriobacteria , orders of Desulfovibrionales and Lactobacillales, the family of Eggerthellaceae , the genera Enterococcus, Lactobacillus , Streptococcus , Sutterella and Uncultured-Rhodospirillales were statistically significant increased in SSc, while the class of Clostridia , the family of Oscillospiraceae and the order UCG-002 were statistically significant increased in VEDOSS (Figure 1). Figure 1. Boxplot showing the results of taxa-level differential abundance analysis between SSC and VEDOSS patients in fecal samples. Plot titles report the shrinked Log2 fold change (according to the DESeq2 function lfcShrink). All results have a p-value < 0.05. VEDOSS patients had significantly higher SF-36-physical component score than SSc, a trend for higher SF-36-mental component summary (MCS), while no difference in the UCLA-GIT2.0 score (Table 1). Table 1. SF 36 and UCLA GIT 2.0 score in VEDOSS and SSc patients VEDOSS (M ± DS) SSc (M ± DS) p-value SF-36-physical component summary 47,8 ± 8,3 40,7 ± 8,3 <0,01 SF-36-mental component summary 46,3 ± 9,2 40,4 ±11,6 0,06 UCLA-GIT 2.0 0,3 ± 0,3 0,4 ± 0,4 NS In SSc patients, we observed a significant positive association between the genus Uncultured - Rhodospirillates and MCS, and between both genera Lactobacillus and Uncultured-Rhodospirillates and UCLA-GIT 2.0 score. In VEDOSS we found a significant positive correlation between both Bacilli class and Lactobacillus genus and MCS. Conclusion Our data show, for the first time, a different microbiota composition in SSc and VEDOSS patients. In particular, we observed an increased abundance of genus Lactobacillus in SSc patients. However, no significant differences in the UCLA GIT score between the two groups were observed, confirming that GI symptoms also affect VEDOSS patients. Both these findings could suggest that the increased Lactobacillus values in SSc patients should raise the suspicion of more severe GIT involvement. This may account for the poor result of a lactobacillus-based probiotic treatment, usually observed in literature. It is necessary to confirm these data on larger groups of patients in the two phases of the disease. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Edda Russo: None declared, Giulio Ghezzi: None declared, Simone Baldi: None declared, Bianca Saveria Fioretto: None declared, Eloisa Romano: None declared, Khadija El Aoufy: None declared, Matteo Ramazzotti: None declared, Irene Rosa: None declared, Gemma Lepri: None declared, Leandro Di Gloria: None declared, Cosimo Bruni Speakers bureau: Eli-Lilly, Consultant of: Boehringer Ingelheim, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC). Educational grants from AbbVie., Daniela Melchiorre: None declared, Serena Guiducci: None declared, Mirko Manetti: None declared, Marco Matucci-Cerinic: None declared, Amedeo Amedei: None declared, Silvia Bellando Randone: None declared.