Ab1143 Characterization of the Fecal Metabolome in Early Systemic Sclerosis

Background: The gastrointestinal tract (GIT) is the second most commonly affected organ system in systemic sclerosis (SSc), affecting 90% of patients.1,2 Despite the high prevalence of GIT involvement, limited effective treatments for gastrointestinal manifestations of the disease exist, in part due to a lack of understanding of the factors that drive this disease process. Recent studies point to the gut microbiome as a potential key mediator in the pathogenesis and progression of GIT involvement in SSc.3 One of the ways in which the gut microbiome may mediate its pathogenic effects is through the production of metabolites. However, no studies have investigated the fecal metabolome in patients with early SSc. Objectives: To compare the fecal metabolome between patients with early SSc and unaffected controls (patients without GI or autoimmune disease). Methods: Stool samples were collected from 115 patients with SSc with a disease duration of Results: The mean age of patients with SSc and healthy controls was 55.3 and 56.7 years, respectively. More women were present in the SSc group compared to the healthy control group (84.9% versus 69.4%). The median disease duration for patients with SSc was 2 years and the majority (67%) of SSc patients had never been exposed to any immunomodulatory therapy. A total of 138 metabolites were detected across the dataset. We identified several fecal metabolites that differed significantly between SSc patients and unaffected controls (Figure 1). Metabolites that were enriched in the feces of patients with SSc included valeric acid isomers (Log2 Fc 0.29, P=0.02) and phosphate (Log2 Fc 0.51, P=0.04). Metabolites that were depleted in patients with SSc included methioninesulfoxide (Log2 Fc -1.0, PConclusion: Methioninesulfoxide was statistically significantly depleted in the feces of a cohort of early SSc patients compared to unaffected controls. Methioninesulfoxide is formed when methionine is oxidized by reactive oxygen species. Previous studies have shown a correlation between the gut microbiome and fecal metabolites in other diseases such as pulmonary fibrosis4 and inflammatory bowel disease5. In future studies, we aim to determine whether certain metabolites such as methioninesulfoxide correlate with the abundance of specific bacterial genera and GIT symptoms in patients with SSc. REFERENCES: 1 Zhu, J. et al. Curr Treat Options in Rheum (2019); 5, 11–19. 2 Andréasson, K. et al. ACR Open Rheumatology (2022); 4(5), 417–425. 3 Plichta, D.R. et al. Genome Med (2021); 13, 35. 4 Gong, G. et al. Life Sciences (2021); 264. 5 Duboc, H. et al. Gut (2013); 62(4), 531–539. Acknowledgements: NIL. Disclosure of Interests: Arissa Young: None declared, Kristofer Andréasson Johnson & Johnson Innovative Medicine, Nedas Matulionis: None declared, Blake Wilde: None declared, Jonathan Jacobs: None declared, Heather Christofk Pelage Pharmaceuticals, Faeth Therapeutics, Pelage Pharmaceuticals, Elizabeth Volkmann Boehringer Ingelheim, GSK, Boehringer Ingelheim, Prometheus, Horizon.