There is a growing understanding of the mechanisms by which the influence of the microbiota projects beyond sites of primary mucosal occupation to other human body systems. Bacteria present in the intestinal tract exert a profound effect on the host immune system, both locally and at distant sites. The oral cavity has its own characteristic microbiota, which concentrates in periodontal tissues and is in close association with a permeable epithelium. In this review we examine evidence which supports a role for the microbiome in the aetiology of rheumatic disease. We also discuss how changes in the composition of the microbiota, particularly within the gastrointestinal tract, may be affected by genetics, diet, and use of antimicrobial agents. Evidence is presented to support the theory that an altered microbiota is a factor in the initiation and perpetuation of inflammatory diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA), and inflammatory bowel disease (IBD). Mechanisms through which the microbiota may be involved in the pathogenesis of these diseases include altered epithelial and mucosal permeability, loss of immune tolerance to components of the indigenous microbiota, and trafficking of both activated immune cells and antigenic material to the joints. The potential to manipulate the microbiome, by application of probiotics and faecal microbial transplant (FMT), is now being investigated. Both approaches are in their infancy with regard to management of rheumatic disease but their potential is worthy of consideration, given the need for novel therapeutic approaches, and the emerging recognition of the importance of microbial interactions with human hosts.

Persister cells represent a multidrug-tolerant (MDT), physiologically distinct subpopulation of bacteria. The ability of these organisms to survive lethal antibiotic doses raises concern over their potential role in chronic disease, such as recurrent urinary tract infection (RUTI). Persistence is believed to be conveyed through global metabolic dormancy, which yields organisms unresponsive to external stimuli. However, recent studies have contested this stance. Here, various antibiotics that target different cellular processes were used to dissect the activity of transcription, translation, and peptidoglycan turnover in persister cells. Differential susceptibility patterns were found in type I and type II persisters, and responses differed between Staphylococcus saprophyticus and Escherichia coli uropathogens. Further, SOS-deficient strains were sensitized to ciprofloxacin, suggesting DNA gyrase activity in persisters and indicating the importance of active DNA repair systems for ciprofloxacin tolerance. These results indicate that global dormancy per se cannot sufficiently account for antibiotic tolerance. Rather, the activity of individual cellular processes dictates multidrug tolerance in an antibiotic-specific fashion. Furthermore, the susceptibility patterns of persisters depended on their mechanisms of onset, with subinhibitory antibiotic pretreatments selectively shutting down cognate targets and increasing the persister fraction against the same agent. Interestingly, antibiotics targeting transcription and translation enhanced persistence against multiple agents indirectly related to these processes. Conducting these assays with uropathogenic E. coli isolated from RUTI patients revealed an enriched persister fraction compared to organisms cleared with standard antibiotic therapy. This finding suggests that persister traits are either selected for during prolonged antibiotic treatment or initially contribute to therapy failure.

Background. A loss of mucosal tolerance to the resident microbiome has been postulated in the aetiopathogenesis of spondyloarthritis, thus the purpose of these studies was to investigate microbial communities that colonise the oral cavity of patients with axial spondyloarthritis (AxSpA) and to compare these with microbial profiles of a matched healthy population.Methods. Thirty-nine participants, 17 patients with AxSpA and 22 age and gender-matched disease-free controls were recruited to the study. For patients with AxSpA, disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants underwent a detailed dental examination to assess oral health, including the presence of periodontal disease assessed using probing pocket depth (PPD). Plaque samples were obtained and their bacterial populations were profiled using Ion Torrent sequencing of the V6 region of the 16S rRNA gene.Results.Patients with AxSpA had active disease (BASDAI 4.1 ± 2.1 [mean ± SD]), and a significantly greater prevalence of periodontitis (PPD ≥ 4 mm at ≥4 sites) than controls. Bacterial communities did not differ between the two groups with multiple metrics of α and β diversity considered. Analysis of operational taxonomic units (OTUs) and higher levels of taxonomic assignment did not provide strong evidence of any single taxa associated with AxSpA in the subgingival plaque.Discussion. Although 16S rRNA gene sequencing did not identify specific bacterial profiles associated with AxSpA, there remains the potential for the microbiota to exert functional and metabolic influences in the oral cavity which could be involved in the pathogenesis of AxSpA.

Background A wealth of data supports a role for the microbiome in the pathogenesis of spondyloarthtritis (SpA). To date, studies have concentrated on the intestinal tract, which harbours the largest and most diverse microbiota. However, the oral microbiota is also notable in its diversity and has recently been the focus of interest as a potential factor in the pathogenesis of rheumatoid arthritis. Recent studies have demonstrated a higher prevalence of periodontitis in patients with ankylosing spondylitis, raising the possibility that exposure to the oral microbiome through a compromised mucosal barrier may be a factor in the pathogenesis of SpA. Objectives To investigate the oral cavity as a site of chronic inflammation in axial spondyloarthritis (AxSpA) and to compare profiles of microbial communities which colonise the oral cavity in health and AxSpA. Methods Thirty nine participants, 17 with AxSpA and 22 age and gender matched, disease free controls, were recruited. Disease activity in patients with AxSpA was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and CRP. All participants underwent a detailed dental examination including assessment of probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), plaque index, oral mucosal conditions, and caries status. Plaque samples were obtained and their bacterial populations were profiled using Ion Torrent sequencing of the V6 region of the 16S rRNA gene. Results Patients with AxSpA had active disease (BASDAI Mean ± SD 4.1±2.1) and had significantly greater prevalence of both periodontitis (PPD≥4mm at ≥4 sites) and a higher plaque index than controls (P=0.008 and P=0.006 respectively). Analysis of bacterial communities showed no difference between AxSpA patients and healthy controls, either in their overall within sample organism diversity or in community structure between groups. However, analysis at the level of operational taxonomic units (OTU) demonstrated a significant association between AxSpA and several bacteria including Campylobacter spp. and Actinomycetes spp. Additionally, certain OTUs were present in higher relative abundances in patients with active AxSpA (see Table). Table 1. Pearson's correlation of OTUs whose abundance is significantly associated (p<0.05) with disease activity, in AxSpA (BASDAI and CRP) OTU p-value r Taxonomic assignment BASDAI correlations  8 0.012 0.594 Rothia dentocariosa  23 0.016 −0.575 Capnocytophaga leadbetteri  0 0.018 0.564 Corynebacterium matruchotii CRP correlations  84 0.004 0.657 Leptotrichia trevisanii  136 0.040 −0.502 Selenomonasspp.  64 0.049 0.485 Fusobacterium nucleatum *FDR corrected p<0.05. Conclusions Patients with AxSpA have a higher prevalence of periodontitis. Analysis of plaque communities suggests that certain bacteria are more prevalent in the periodontal tissues of patients with AxSpA and associates with active disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3406