Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies

Objective: Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods: Mendelian randomization (MR) is a type of instrumental variables (IVs) analysis; MR follows the Mendelian genetic rule of “parental alleles are randomly assigned to offspring” and takes genetic variation as IVs to infer the causal association between exposure factors and study outcome in observational studies. Genome-wide association study (GWAS) summary data of AS were from the FinnGen consortium, and the gut microbiota (Bacteroides, Streptococcus, Proteobacteria, Lachnospiraceae) were from the MiBioGen consortium. The TwoSampleMR and MRPRESSO packages of the R were used to perform a two-sample MR study. Random-effects inverse variance weighted (IVW) was the main analysis method, and MR Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We examined heterogeneity and horizontal pleiotropy, and examined whether the analysis results were influenced by a single SNP. We applied radial variants of the IVW and MR-Egger model for the improved visualization of the causal estimate. We further examined the causal relationship between AS and gut microbiota, and the robustness of the analysis results. Finally, we performed maximum likelihood, penalized weighted median, and IVW (fixed effects) to further identify the potential causal association. Results: The random-effects IVW results showed that Bacteroides (p = 0.965, OR 95% confidence interval [CI] = 0.990 [0.621–1.579]), Streptococcus (p = 0.591, OR 95% CI = 1.120 [0.741–1.692]), Proteobacteria (p = 0.522, OR 95% CI = 1.160 [0.737–1.826]), and Lachnospiraceae (p = 0.717, OR 95% CI = 1.073 [0.732–1.574]) have no genetic causal relationship with AS. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. Conclusions: This study showed that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae, four common gut microbiotas associated with AS, had no causal relationship with AS at the genetic level. This study makes a positive contribution to the genetics of AS, but the insufficient number of gut microbiota included is a limitation.

/pdf/no-evidence-of-a-genetic-causal-relationship-between-3vbsbntr.pdf

No Evidence of a Genetic Causal Relationship between Ankylosing Spondylitis and Gut Microbiota: A Two-Sample Mendelian Randomization Study

Interactions between NSAIDs, opioids and the gut microbiota - Future perspectives in the management of inflammation and pain.

Rheumatoid arthritis is a chronic systemic immune-mediated disease caused by genetic and environmental factors. It is often characterized by the generation of autoantibodies that lead to synovial inflammation and eventual multi-joint destruction. A growing number of studies have shown significant differences in the gut microbiota composition of rheumatoid arthritis (RA) patients compared to healthy controls. Environmental factors, and changes in diet and nutrition are thought to play a role in developing this dysbiosis. This review aims to summarize the current knowledge of intestinal dysbiosis, the role of nutritional factors, and its implications in the pathogenesis of rheumatoid arthritis and autoimmunity. The future direction focuses on developing microbiome manipulation therapeutics for RA disease management.

/pdf/role-of-intestinal-dysbiosis-and-nutrition-in-rheumatoid-1g5dj55e.pdf

Role of Intestinal Dysbiosis and Nutrition in Rheumatoid Arthritis

Spondyloarthritis (SpA) is a family of chronic inflammatory diseases, being the most prevalent ankylosing spondylitis (AS) and psoriatic arthritis (PsA). These diseases share genetic, clinical and immunological features, such as the implication of human leukocyte antigen (HLA) class I molecule 27 (HLA-B27), the inflammation of peripheral, spine and sacroiliac joints and the presence of extra-articular manifestations (psoriasis, anterior uveitis, enthesitis and inflammatory bowel disease). Monocytes and macrophages are essential cells of the innate immune system and are the first line of defence against external agents. In rheumatic diseases including SpA, the frequency and phenotypic and functional characteristics of both cell types are deregulated and are involved in the pathogenesis of these diseases. In fact, monocytes and macrophages play key roles in the inflammatory processes characteristics of SpA. The aim of this review is analysing the characteristics and functional roles of monocytes and macrophages in these diseases, as well as the impact of different current therapies on these cell types.

/pdf/monocytes-and-macrophages-in-spondyloarthritis-functional-28yniv1y.pdf

Monocytes and Macrophages in Spondyloarthritis: Functional Roles and Effects of Current Therapies

Gut microbiota changes in patients with spondyloarthritis: A systematic review.

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Gut microbiota changes in patients with spondyloarthritis: A systematic review.