Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
The gastro-intestinal tract (GIT) is frequently involved in Systemic sclerosis (SSc). Perturbation in the gut microbiota may affect the body well-being and function and intestinal disbiosis has been associated with a number of autoimmune diseases, including SSc. To date no attempt has been made to characterize the functional consequences of intestinal disbioisis in SSc and autoimmunity.
A total of 59 SSc patients and 28 healthy controls (HCs) were included. Intestinal microbiota was studied via 16s-RNA sequencing on stool samples; in parallel, plasma metabolites were analyzed by high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry (HPLC-MS-ESI-QTOF). Interaction models capable of explaining the disease were built via data mining algorithms with internal validation (20 x 10-fold cross-validation) and feature selection. Microbic and metabolic results were correlated by means of Spearman’s rho and results corrected via 100K-fold permutation testing. The severity of intestinal symptoms was assessed via the UCLA GIT questionnaire.
random forest model showed that HCs and SSc patients differ at the genus taxonomic rank (AUROC = 0.706 ± 0.023). Model reduction identified 9 genera relevant to the disease status (AUROC = 0.711 ± 0.042). A naïve Bayes algorithm found a unique metabolic pattern associated with SSc (AUROC = 0.707 ± 0.029) with just 17 relevant metabolites after feature selection (AUROC = 0.744 ± 0.029). Cross correlation between the 9 genera and the 17 metabolites (Figure, left panel) found significant interactions between desulfovibrio and alpha-N-Phenylacetyl-L-glutamine (rho = 0.389, pc = 0.03) and 2,4-dinitrobenzenesulfonic acid (rho = 0.39, pc = 0.029). Gut microbiota of SSc patients was capable of explaining 12.7 ± 4.1% of the variance of GIT scores. A model of 10 bacteria could jointly discriminate HCs and SSc patients with or without intestinal involvement (weighted AUROC = 0.679 ± 0.021). Among these bacteria, desulfovibrio was significantly associated with the presence of intestinal involvement (figure, right panel).
SSc patients present unique microbic and metabolic fingertips. SSc-related disbiosis is characterized by an increase in pro-inflammatory microbial groups which compete with commensal bacteria. This microbiomic shift may promote the accumulation of metabolites, including a a sulfonate compound which has direct pro-inflammatory and immuno-modulating properties and that may serve as electron acceptor in anaerobic respiration of desulfovibrio strains. The toxic end-product of desulfovibrio respiratory metabolism (hydrogen sulfide) may contribute to intestinal damage and altered motility.
This work received support from the EU/EFPIA IMI Joint Undertaking PRECISESADS grant n° 115565. www.precisesads.eu
To cite this abstract in AMA style:Bellocchi C, Fernández-Ochoa A, Montanelli G, Vigone B, Santaniello A, Milani C, Quirantes-PIné R, Borras Linares I, Ventura M, Segura Carretero A, Alarcón-Riquelme M, Beretta L. Microbial and Metabolic MULTI-Omic Correlations in Systemic Sclerosis Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/microbial-and-metabolic-multi-omic-correlations-in-systemic-sclerosis-patients/. Accessed September 25, 2021.
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