Disease Features and Gastrointestinal Microbial Composition in Systemic Sclerosis Patients from Two Independent Cohorts
| Autor: | Meifang Wu, Elizabeth R. Volkmann, Kristofer Andréasson, Roger Hesselstrand, Jonathan P. Jacobs, Philip J. Clements, Natalie Howlett, S. Melanie Lee, Venu Lagishetty |
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| Rok vydání: | 2021 |
| Předmět: |
History
medicine.medical_specialty Polymers and Plastics business.industry Interstitial lung disease Disease medicine.disease Institutional review board Industrial and Manufacturing Engineering Internal medicine Cohort Small intestinal bacterial overgrowth Medicine Microbiome Business and International Management business Dysbiosis Rheumatism |
| Zdroj: | SSRN Electronic Journal. |
| ISSN: | 1556-5068 |
| Popis: | Background: Previous studies have demonstrated alterations in gastrointestinal (GI) microbiota of patients with systemic sclerosis (SSc). However, these prior studies did not include patients with early SSc, nor examine the impact of disease features on microbial composition. The present study investigated the relationship between SSc features and GI microbiota using two independent, international cohorts. Methods: Prospective SSc patients from Lund University (LU), Sweden, the University of California, Los Angeles (UCLA) and control subjects provided stool specimens for 16S rRNA sequencing. Beta diversity analyses were performed to assess the relationship between disease features and GI microbiota. Multivariate negative binomial models identified differentially abundant genera between groups. Findings: Compared with LU-controls (N=85), early-stage LU-SSc patients (N=106; median disease duration of 2·0 years) had lower abundance of commensal genera (e.g., Faecalibacterium) and increased abundance of pathobiont genera (e.g., Desulfovibrio. Disease features associated with microbial composition (beta diversity) in the LU-SSc patients and UCLA-SSc patients (N=71) included disease duration (P=0·0016), interstitial lung disease (P=0·0030), small intestinal bacterial overgrowth (P=0·0020), and immunosuppression use (P=0·014). After adjusting for these factors, the UCLA-SSc cohort had increased abundance of several pathobiont genera (e.g., Streptococcus) compared with the LU-SSc cohort. Interpretation: This study provides the first evidence that dysbiosis is present early in the SSc disease course. Specific disease features were independently associated with fecal microbial composition in Swedish and American patients. After controlling for these factors, the abundance of pathobiont bacteria differed between cohorts, suggesting that environmental factors affecting the GI microbiota should be considered in future SSc studies. Funding: NHLBI (K23 HL150237-01; ERV), VA (CDA2 IK2CX001717; JPJ), NIH (T32 DA024635; SML), Elizabeth Wallace (ERV); The Swedish Medical Society (KA), The Swedish Rheumatism Association (KA), Stiftelsen Ulla och Roland Gustafssons Donationsfond (KA) and Anna-Greta Crafoords stiftelse (KA). Declaration of Interest: ERV reports the following financial relationships outside of the submitted work: Consulting (Boehringer Ingelheim, Forbius); Research grants (Kadmon, Forbius, Corbus). All other authors have nothing to declare. Ethical Approval: The UCLA Institutional Review Board (#13-001089) and the Regional Ethics Review Board, Lund, Sweden (#2011-596) approved the study protocol and written informed consent was obtained from each participant. |
| Databáze: | OpenAIRE |
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