Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: In the Rheumatoid Arthritis (RA) prodrome, genetic predisposition intersects with environmental risk factors, such as smoking, periodontal disease and respiratory infection, however no studies to date compare the microbiomes of at-risk first-degree relatives (FDR) with Healthy controls (HC) and RA probands. We hypothesized that specific microbial taxa (operational taxonomic units, OTUs) from the oral and fecal microbiota differentiate between RA and HC, and that FDR segregate based on similarity with RA patients or HC.
Methods: We chacterized a prospective cohort of RA probands, FDR and HC. Probands met ACR 2010 criteria and/or had a confirmed RA diagnosis. FDRs included parents, full siblings or offspring of an RA proband; HC were drawn from the community. From all individuals, we obtained demographics, medical history, epidemiological questionnaires and tissue collections. After DNA extraction from tongue and fecal swabs, we undertook targeted 16S rRNA gene sequencing using Illumina MiSeq then used standard QIIME workflows, visualizations with the Phyloseq R package and multivariate statistical analysis using the mixOmics R package.
Results: 116 RA patients, 63 FDR and 43 HC matched for age and gender were recruited. 56% and 57% of RA, 4% and 49% of FDR and 0% and 37% of HCs were ACPA+ and shared epitope positive respectively. 47% RA patients, 30% FDR and 37% HC had ever smoked. Based on multivariate analyses, oral and faecal microbiota were altered in RA relative to HC. The oral community profile in RA was enriched in opportunistic pathogens including Streptococcus, Veillonella, Staphylococcus and Camplylobacter spp., Propionibacterium acnes and Prevotella melaninogenica. The fecal community profile in RA patients was enriched in Bacteroides, Enterococcus and Pseudomonas spp., while in HC in Clostridiales, particularly members of the Lachnospiraceae. By univariate analysis, the abundance particular oral and fecal OTUs was strongly associated with environmental risk factors. For example, a fecal Peptococcus sp. was associated with smoking history, dental history and a history of respiratory infection. The oral and faecal OTU profile of some FDRs segregated with the RA patients and some segregated with HC.
Conclusion: We demonstrate distinct oral and fecal community profiles in RA patients relative to HC, which are influenced by environmental risk factors such as smoking, dental or respiratory infection. The oral and faecal associated microbiota of individual FDRs segregates either with RA or HC subjects. Thus, compound genetic and environmental risks may promote inhospitable mucosal environments for commensals abundant in HC, creating niches for opportunistic pathogens before and after the development of RA.
To cite this abstract in AMA style:Benham H, Maradana M, Lakis VA, O Cuiv P, Wood J, Nagl L, Rammouth N, Owens C, Daly J, Lachner N, Morrison M, Hugenholtz P, Lê Cao KA, Thomas R. Distinct Oral and Fecal Community Profiles Enriched in Opportunistic Pathogens in RA Patients and First Degree Relatives Are Influenced By Environmental Risk Factors, Including Smoking, Dental History and Lung Infection [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/distinct-oral-and-fecal-community-profiles-enriched-in-opportunistic-pathogens-in-ra-patients-and-first-degree-relatives-are-influenced-by-environmental-risk-factors-including-smoking-dental-history/. Accessed January 25, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinct-oral-and-fecal-community-profiles-enriched-in-opportunistic-pathogens-in-ra-patients-and-first-degree-relatives-are-influenced-by-environmental-risk-factors-including-smoking-dental-history/