Abstract

Objectives: Describe the intestinal microbiome profile in RA patients and analyze the mechanisms through which intervenes in the pathogenesis RA. Methods: Design: Controlled, observational, cross-sectional study of established RA cohort. Patients: Forty consecutive RA patients (ACR/EULAR 2010 criteria) >16 years, selected from a prospective inception cohort (2007-2011) and 40 sex-age matched healthy controls. Protocol: Cases and controls were evaluated by a rheumatologist. Clinical data of disease activity were collected during the follow-up and analytical values were determined. Fecal samples were frozen within 24 hours of collection. Main outcome: Fecal samples exam. Microbial DNA was extracted from fecal samples using QIAamp DNA stool Mini kit. The concentration and quality of DNA was determined by Nanodrop. Secondary Other variables: Demographic, clinical-analytical and therapies (DMARDs). Statistical analysis: Analysis of microbiota prole: UniFracPCoA (Principal Coordinate Analysis) was performed with the abundance data of operational taxonomic units (OTU) by means of the variancecovariance matrix implemented in Quantitative Insights Into Microbial Ecology(QIIME). The relative abundance of each OTU (taxa) was compared using a Wilcoxon test. The variations of abundance and diversity were compared by ANOSIM pathway. The calculation of α and β-diversity was carried out using QIIME. Results: Most of subjects were women (75%) (table). In RA patients, the average DAS28 was 3.6. β-diversity data showed that patients tend to dier from healthy subjects according to their microbiota (p = 0.07). Patients with RA exhibited decreased gut microbiome diversity compared with controls, although was not statistically signicant. Regarding in species richness, the analysis suggested an increase of the Collinsella aerofaciens species and enterococcus genera in patients compared with controls. Likewise, an increase of arginine deaminase activity was observed, which belonged, in approximately 90%, to the RA genes of the genus Collinsela.The multivariate analysis identified ACPA positive (s [95% CI], 0.33 [27.4-390]), smoking (0.3 [8.8-256.4]) and age (-0.3 [27.4-390.0]) as factors associated with Collinsela.Also, we observed a decrease in other bacterial lineages. On the other hand, RA patients showed an altered metabolic capacity for the transport of zinc and copper. Conclusion: These observations suggest a dysbiosis in RA patients, resulting from the abundance of certain bacterial (i.e Collinsela) and decrease of other bacterial lineages. These alterations could inuence in a signicant way in the perpetuation of the autoimmunity of the disease. Disclosure of Interests: Natalia Mena-Vazquez: None declared, Patricia Ruiz-Limon: None declared, Isabel Moreno-Indias: None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Francisco Jose Tinahones: None declared, Antonio Fernandez-Nebro: None declared

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