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Journal ArticleDOI: 10.1093/RHEUMATOLOGY/KEAA835

The oral and gut microbiome in rheumatoid arthritis patients: a systematic review

02 Mar 2021-Rheumatology (Oxford Academic)-Vol. 60, Iss: 3, pp 1054-1066
Abstract: Background Recently, researchers have proposed a possible relationship between RA and the microbiome of the oral cavity and gut. However, this relation has not been systematically established. Herein, we conducted a comprehensive review of the pertinent literature to describe this possible association. Methods We systematically performed searches in databases, namely EMBASE, the Cochrane Library, and PubMed, from inception to 7 June 2020 to identify case-control studies that compared the oral and gut microbiome in adult RA patients with those of controls. The primary outcome was specific bacterial changes between RA and controls. The secondary outcome was microbial diversity changes between RA and controls. Results In total, 26 articles were considered eligible for inclusion and reported some differences. Therein, ≥3 articles reported decreased Faecalibacterium in the gut of early-RA (ERA)/RA patients compared with healthy controls (HCs). Also, ≥3 articles reported decreased Streptococcus and Haemophilus and increased Prevotella in the oral cavity of ERA/RA patients compared with HCs. In addition, some Prevotella species, including P. histicola and P. oulorum, showed increased trends in RA patients' oral cavity, compared with HCs. The α-diversity of the microbiome was either increased or not changed in the oral cavity of RA patients, but it was more commonly either decreased or not changed in the gut of RA patients. Conclusions In this systematic review, we identified the microbiome associated with RA patients in comparison with controls. More research is needed in the future to find the deep relationship between RA and the microbiome.

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Topics: Microbiome (55%)
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6 results found


Open accessJournal ArticleDOI: 10.3390/MICROORGANISMS9051070
Alok Kumar Paul1, Anita Paul1, Rownak Jahan1, Khoshnur Jannat1  +6 moreInstitutions (4)
16 May 2021-
Abstract: Rheumatoid arthritis is a chronic autoimmune disorder that can lead to disability conditions with swollen joints, pain, stiffness, cartilage degradation, and osteoporosis. Genetic, epigenetic, sex-specific factors, smoking, air pollution, food, oral hygiene, periodontitis, Prevotella, and imbalance in the gastrointestinal microbiota are possible sources of the initiation or progression of rheumatoid arthritis, although the detailed mechanisms still need to be elucidated. Probiotics containing Lactobacillus spp. are commonly used as alleviating agents or food supplements to manage diarrhea, dysentery, develop immunity, and maintain general health. The mechanism of action of Lactobacillus spp. against rheumatoid arthritis is still not clearly known to date. In this narrative review, we recapitulate the findings of recent studies to understand the overall pathogenesis of rheumatoid arthritis and the roles of probiotics, particularly L. casei or L. acidophilus, in the management of rheumatoid arthritis in clinical and preclinical studies.

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2 Citations


Open accessJournal ArticleDOI: 10.3390/MICROORGANISMS9091930
Yi-Wen Tsai1, Jia-Ling Dong2, Yun-Jie Jian2, Shin-Huei Fu2  +6 moreInstitutions (3)
10 Sep 2021-
Abstract: Autoimmunity is a complex and multifaceted process that contributes to widespread functional decline that affects multiple organs and tissues. The pandemic of autoimmune diseases, which are a global health concern, augments in both the prevalence and incidence of autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The development of autoimmune diseases is phenotypically associated with gut microbiota-modulated features at the molecular and cellular levels. The etiology and pathogenesis of autoimmune diseases comprise the alterations of immune systems with the innate and adaptive immune cell infiltration into specific organs and the augmented production of proinflammatory cytokines stimulated by commensal microbiota. However, the relative importance and mechanistic interrelationships between the gut microbial community and the immune system during progression of autoimmune diseases are still not well understood. In this review, we describe studies on the profiling of gut microbial signatures for the modulation of immunological homeostasis in multiple inflammatory diseases, elucidate their critical roles in the etiology and pathogenesis of autoimmune diseases, and discuss the implications of these findings for these disorders. Targeting intestinal microbiome and its metabolomic associations with the phenotype of autoimmunity will enable the progress of developing new therapeutic strategies to counteract microorganism-related immune dysfunction in these autoimmune diseases.

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Topics: Autoimmunity (51%), Gut flora (51%), Immune system (50%)

1 Citations



Open accessJournal ArticleDOI: 10.3390/IJMS221910576
Eui-Jong Kwon1, Ji Hyeon Ju1Institutions (1)
Abstract: Rheumatoid arthritis (RA) is caused by prolonged periodic interactions between genetic, environmental, and immunologic factors. Posttranslational modifications (PTMs) such as citrullination, carbamylation, and acetylation are correlated with the pathogenesis of RA. PTM and cell death mechanisms such as apoptosis, autophagy, NETosis, leukotoxic hypercitrullination (LTH), and necrosis are related to each other and induce autoantigenicity. Certain microbial infections, such as those caused by Porphyromonasgingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri, can induce autoantigens in RA. Anti-modified protein antibodies (AMPA) containing anti-citrullinated protein/peptide antibodies (ACPAs), anti-carbamylated protein (anti-CarP) antibodies, and anti-acetylated protein antibodies (AAPAs) play a role in pathogenesis as well as in prediction, diagnosis, and prognosis. Interestingly, smoking is correlated with both PTMs and AMPAs in the development of RA. However, there is lack of evidence that smoking induces the generation of AMPAs.

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Topics: Citrullination (57%)

Open accessJournal ArticleDOI: 10.3389/FNUT.2021.646819
Dan-Ping Li1, Dan-Ping Li2, Min Cui1, Fang Tan1  +3 moreInstitutions (2)
Abstract: Inflammatory bowel disease (IBD) is a serious hazard to public health, but the precise etiology of the disease is unclear. High intake of red meat diet is closely related to the occurrence of IBD. In this study, we investigated whether the high intake of red meat can increase the sensitivity of colitis and the underlying mechanism. Mice were fed with different levels of red meat for 8 weeks and then the colonic contents were analyzed by 16S rRNA sequencing. Then 3% dextran sulfate sodium was used to induce colitis in mice. We observed the severity of colitis and inflammatory cytokines. We found that high-dose red meat caused intestinal microbiota disorder, reduced the relative abundance of Lachnospiraceae_NK4A136_group, Faecalibaculum, Blautia and Dubosiella, and increased the relative abundance of Bacteroides and Alistipes. This in turn leads to an increase in colitis and inflammatory cytokine secretion. Moreover, we found that high red meat intake impaired the colon barrier integrity and decreased the expression of ZO-1, claudin, and occludin. We also found high red meat intake induced the production of more inflammatory cytokines such as IL-1β, TNF-α, IL-17, and IL-6 and inflammatory inducible enzymes such as COX-2 and iNOS in dextran sulfate sodium-induced colitis. These results suggest that we should optimize the diet and reduce the intake of red meat to prevent the occurrence of IBD.

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Topics: Colitis (57%), Red meat (57%), Inflammatory bowel disease (57%) ... show more

References
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53 results found


Open accessJournal ArticleDOI: 10.1038/NATURE11234
Curtis Huttenhower1, Curtis Huttenhower2, Dirk Gevers1, Rob Knight3  +250 moreInstitutions (42)
14 Jun 2012-Nature
Abstract: The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

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Topics: Human Microbiome Project (72%), Oral Microbiome (65%), Microbiome (64%) ... show more

6,805 Citations


Open accessJournal ArticleDOI: 10.1126/SCIENCE.1110591
10 Jun 2005-Science
Abstract: The human endogenous intestinal microflora is an essential “organ” in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.

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Topics: Intestinal mucosa (60%), Flora (microbiology) (50%)

6,268 Citations


Journal ArticleDOI: 10.1056/NEJMRA1004965
Iain B. McInnes1, Georg SchettInstitutions (1)
Abstract: The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality.

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Topics: Arthritis (65%), Rheumatoid arthritis (54%), Antirheumatic Agents (53%)

3,296 Citations


Open accessJournal ArticleDOI: 10.1038/NATURE12873
Yukinori Okada1, Yukinori Okada2, Di Wu1, Di Wu2  +112 moreInstitutions (39)
20 Feb 2014-Nature
Abstract: A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

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1,556 Citations


Open accessJournal ArticleDOI: 10.1038/NG.582
01 Jun 2010-Nature Genetics
Abstract: To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.

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1,172 Citations