Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis

Tong, Yanli; Zheng, Linlin; Qing, Pingying; Zhao, Hua; Li, Yanhong; Su, Lin‐Chong; Zhang, Qiuping; Zhao, Yi; Luo, Yubin; Liu, Yi

doi:10.3389/fcimb.2019.00475

Cited by 76 publications

(69 citation statements)

References 30 publications

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“…This is in line with other studies that investigated the oral microbial diversity between patients with chronic inflammatory diseases, i.e. rheumatoid arthritis, and healthy controls (Scher et al, 2012;Tong et al, 2019). Differential abundance analysis revealed several taxa to be associated with or depleted in JIA.…”

Section: Microbial Profile Bacterial Diversity and Differentially Absupporting

confidence: 90%

Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study

Frid

Baraniya

Halbig

et al. 2020

Front. Cell. Infect. Microbiol.

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Section: Microbial Profile Bacterial Diversity and Differentially Absupporting

confidence: 90%

Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study

Frid

Baraniya

Halbig

et al. 2020

Front. Cell. Infect. Microbiol.

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“…We previously reported a lower bacterial diversity in saliva microbiome in high-risk individuals for RA [16]. Consistent with the change in saliva, there was a signi cant decrease in the intestinal bacterial diversity in Pre-RA individuals compared with HC.…”

Section: Discussionsupporting

confidence: 80%

“…Although the 'mucus origins hypothesis' has been raised based on ndings of mucosal in ammation in early RA patients, it is still unclear how the microbial changes and mucosal in ammation are contributory to RA pathogenesis during the preclinical stage. In fact, we have already noticed that oral microbial dysbiosis occurs in early RA patients [16]. D Alpizar-Rodriguez et al reported the difference in intestinal microbiome in European populations with high risk for RA [17].…”

Section: Introductionmentioning

confidence: 93%

Gut Microbiota Dysbiosis in High-Risk Individuals For Rheumatoid Arthritis Triggers Mucosal Immunity Perturbation and Promotes Arthritis in Mice

Tong

Tang

et al. 2020

Preprint

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Background: Intestinal microbial dysbiosis in patients with rheumatoid arthritis (RA) is associated with enhanced inflammation in the joint. Recent studies indicate intestinal microbiota changes prior to clinical signs of arthritis in the joints. However, it remains undefined whether gut microbiota dysbiosis is triggering the initiation and progression of RA during the preclinical stages. Here, we describe the gut microbiome characteristics in preclinical high-risk individuals for RA, and investigate their consequences on the mucosal immunes system and involvement in the pathogenesis of arthritis.Results: 16S rRNA sequencing was performed on faeces from human participants, comprising preclinical high-risk for RA individuals (Pre-RA, n=53), who were anti-citrullinated protein antibodies positive, established RA patients (RA, n=30) and healthy individuals (HCs, n=38). Pre-RA individuals showed lower fecal microbial diversity comparing with HCs. The bacterial community structure dynamically shifted from HCs to Pre-RA individuals and to RA patients, with the relative abundance changes of genera including Bacteroides, Ruminiclostridium_5, and Streptococcus. To further decipher the effect of these gut microbiota alterations in mucosal immune response, we transplanted pooled human fecal samples from each group into antibiotics pre-treated mice. The inoculation of faeces from the Pre-RA group increased fluorescent-labelled dextran uptake, decreased ZO-1 gene expression in the intestine, and changed typical microvilli structure of the small intestine of the recipient mice. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer’s patches were also increased in mice following fecal microbiota transplantation (FMT) from Pre-RA and RA compared to HC group. We also applied the collagen induced arthritis (CIA) mice model to test the effect of FTM from Pre-RA individuals on arthritis severity. Importantly, we revealed that the FMT from Pre-RA and RA group similarly enhanced clinical CIA symptom in recipient mice as compared with HC-FMT mice.Conclusions: Gut microbial dysbiosis is already present in high-risk individuals for RA with autoimmune signature. FMT from preclinical individuals triggers the intestinal barrier dysfunction and changed mucosal immunity further contributing to arthritis development.

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“…The 16S rDNA hypervariable V3-V4 region was PCR-ampli ed with the forward primer 338F (5'-ACTCCTACGGGAGGCAGCAG-3') and the reverse primer 806R (5'-GGACTACHVGGGTWTCTAAT-3') using a GeneAmp™ PCR System 9700 (Applied Biosystems, Carlsbad, CA, USA). The parameters of the PCR reactions have been described in a previous study [13]. Each PCR reaction was performed in triplicate and all resulting PCR products were extracted from 2% agarose gels and then further puri ed using the AxyPrep DNA Gel Extraction Kit (Axygen Biosciences, Union City, CA, USA) and quanti ed using a QuantiFluor® Single-Tube Fluorometer (Promega Corporation, Madison, WI, USA) in accordance with the manufacturers' instructions.…”

Section: Dna Extraction Ampli Cation and High-throughput Sequencingmentioning

confidence: 99%

“…Raw fastq les were quality-ltered using the Trimmomatic read trimming tool (https://kbase.us/) and merged using FLASH software (version 1.2.11; https://ccb.jhu.edu/software/FLASH/index.shtml) in accordance with the criteria described in a previous report [13]. After trimming, operational taxonomic units (OTUs) were clustered at a similarity cutoff value of 97% using the UPARSE algorithm (version 7.1;…”

Section: Data Processing and Bioinformatics Analysismentioning

confidence: 99%

Shifts in the bacterial community of supragingival plaque related to metabolic associated fatty liver disease

Zhao

Yuan

Wang

et al. 2020

Preprint

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Background Metabolic-associated fatty liver disease (MAFLD), also known as the hepatic manifestation of metabolic disorders, has become one of the most common chronic liver diseases worldwide. The associations between some oral resident microbes and MAFLD have been described. However, changes to the oral microbial community in patients with MAFLD remain unknown. Methods In this study, variations to the supragingival microbiota of MAFLD patients were identified. The microbial genetic profile of supragingival plaque samples from 24 MAFLD patients and 22 healthy participants were analyzed by 16S rDNA sequencing and bioinformatics analysis. Clinical variables, including indicators of insulin resistance, obesity, blood lipids, and hepatocellular damage, were evaluated with laboratory tests and physical examinations. Results The results showed that the diversity of the supragingival microbiota in MAFLD patients was significantly higher than that in healthy individuals. Weighted UniFrac principal coordinates analysis and partial least squares discriminant analysis showed that the samples from the MAFLD and control groups formed separate clusters (Adonis, P = 0.0120). There were 27 taxa with differential distributions (linear discriminant analysis, LDA༞2.0) between two groups, among which Actinomyces and Prevotella 2 spp. were over-represented in the MAFLD group with highest LDA score, while Neisseria and Bergeyella spp. were more abundant in the control group. Co-occurrence networks of the top 50 abundant genera in the two groups suggested that the inter-genera relationships were also altered in the supragingival plaque of MAFLD patients. In addition, as risk factors for the development of MAFLD, insulin resistance was positively correlated with the abundances of Granulicatella, Veillonella, Streptococcus, and Scardovia spp., while obesity was positively correlated to the abundances of Streptococcus, Oslenella, Scardovia, and Selenomonas spp. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to sugar (mainly free sugar) metabolism were enriched in the supragingival plaque of the MAFLD group. Conclusions In conclusion, as compared to healthy individuals, component and interactional dysbioses were observed in the supragingival microbiota of the MAFLD group, which could be further explored as potential oral biomarkers of the MAFLD.

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Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis

Cited by 76 publications

References 30 publications

Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study

Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study

Gut Microbiota Dysbiosis in High-Risk Individuals For Rheumatoid Arthritis Triggers Mucosal Immunity Perturbation and Promotes Arthritis in Mice

Shifts in the bacterial community of supragingival plaque related to metabolic associated fatty liver disease

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