Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthritis

Sandhya, Pulukool; Danda, Debashish; Sharma, Disha; Scaria, Vinod

doi:10.1111/1756-185x.12728

Cited by 46 publications

(45 citation statements)

References 108 publications

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“…It has been hypothesized that dysbiosis of the microbiome could lead to local inflammation, loss of barrier function, and bacterial translocation from mucosa to the bloodstream. Some bacterial cell wall components might molecularly mimic human autoantigens, triggering an immune response also directed against the joint [20, 21]. …”

Section: Risk Factorsmentioning

confidence: 99%

The role of autoantibodies in the pathophysiology of rheumatoid arthritis

2017

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

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Section: Risk Factorsmentioning

confidence: 99%

The role of autoantibodies in the pathophysiology of rheumatoid arthritis

2017

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“…In addition, Prevotella also appears to correlate with other microbial differences between lean and obese adults, associated with both the overall bacterial composition and digestive efficiency (23,24). In contrast to these seemingly positive effects, some clinical studies concluded that elevations in Prevotella may be a signature feature of the dysbiosis seen in autoimmune conditions, such as rheumatoid arthritis (25–27). …”

Section: Introductionmentioning

confidence: 99%

Social Influences on Prevotella and the Gut Microbiome of Young Monkeys

et al. 2017

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Objective Our aim was to evaluate the bacterial profiles of young monkeys as they were weaned into peer groups with a particular focus on Prevotella, an important taxon in both human and nonhuman primates. The weaning of infants and increased social contact with peers is a developmental stage that is likely to affect the gut microbiome. Methods Gut bacteria were assessed in 63 rhesus monkeys living in social groups comprised of 4–7 individuals. Two groups were assessed prospectively on Day 1 and 2 weeks after rehousing away from the mother and group formation. Ten additional groups were assessed at 2 weeks after group establishment. Fecal genomic DNA was extracted and 16S ribosomal RNA sequenced by Illumina MiSeq (5 social groups) and 454-amplicon pyrosequencing (7 social groups). Results Combining weaned infants into small social groups led to a microbial convergence by 2 weeks (p<.001). Diversity analyses indicated more similar community structure within peer groups than across groups (p<.01). Prevotella was the predominant taxon and its abundance differed markedly across individuals. Indices of richness, microbial profiles and less abundant taxa were all associated with the Prevotella levels. Functional KEGG analyses suggested corresponding shifts in metabolic pathways. Conclusions The formation of small groups of young rhesus monkeys was associated with significant shifts in the gut microbiota. The profiles were closely associated with the abundance of Prevotella, a predominant taxon in the rhesus monkey gut. Changes in the structure of the gut microbiome are likely to induce differences in metabolic and physiologic functioning.

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“…Recent findings demonstrate that alteration in the equilibrium among commensal bacteria is associated not only with Inflammatory bowel disease (IBD), allergy, diabetes and celiac disease (Cheng et al, 2013), but also with rheumatoid arthritis (Vaahtovuo et al, 2008; Sandhya et al, 2016; Scher et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Alteration of Fecal Microbiota Profiles in Juvenile Idiopathic Arthritis. Associations with HLA-B27 Allele and Disease Status

et al. 2016

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Alteration of gut microbiota is involved in several chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, and gut microbial “pro-arthritogenic” profiles have been hypothesized. Intestinal inflammation may be involved in spondyloarthropathies and in a subset of patients affected by Juvenile Idiopathic Arthritis (JIA), the most common chronic rheumatic disease of childhood. We compared the fecal microbiota composition of JIA patients with healthy subjects (HS), evaluating differences in microbial profiles between sub-categories of JIA, such as enthesitis-related arthritis (JIA-ERA), in which inflammation of entheses occurs, and polyarticular JIA, non-enthesitis related arthritis (JIA-nERA). Through taxon-level analysis, we discovered alteration of fecal microbiota components that could be involved in subclinical gut inflammation, and promotion of joint inflammation. We observed abundance in Ruminococcaceae in both JIA categories, reduction in Clostridiaceae and Peptostreptococcaceae in JIA-ERA, and increase in Veillonellaceae in JIA-nERA, respectively, compared with HS. Among the more relevant genera, we found an increase in Clostridium cluster XIVb, involved in colitis and arthritis, in JIA-ERA patients compared with HS, and a trend of decrease in Faecalibacterium, known for anti-inflammatory properties, in JIA-nERA compared with JIA-ERA and HS. Differential abundant taxa identified JIA patients for the HLA-B27 allele, including Bilophila, Clostridium cluster XIVb, Oscillibacter, and Parvimonas. Prediction analysis of metabolic functions showed that JIA-ERA metagenome was differentially enriched in bacterial functions related to cell motility and chemotaxis, suggesting selection of potential virulence traits. We also discovered differential microbial profiles and intra-group variability among active disease and remission, suggesting instability of microbial ecosystem in autoimmune diseases with respect to healthy status. Similarly to other chronic autoimmune and inflammatory diseases, different microbial profiles, as observed among different JIA subgroups compared to HS, and potential functional acquisition related to migration, could promote inflammation and contribute to the disease pathogenesis.

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Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthritis

Cited by 46 publications

References 108 publications

The role of autoantibodies in the pathophysiology of rheumatoid arthritis

The role of autoantibodies in the pathophysiology of rheumatoid arthritis

Social Influences on Prevotella and the Gut Microbiome of Young Monkeys

Alteration of Fecal Microbiota Profiles in Juvenile Idiopathic Arthritis. Associations with HLA-B27 Allele and Disease Status

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