Data-driven multiple-level analysis of gut-microbiome-immune-joint interactions in rheumatoid arthritis

Wang, QuanQiu; Xu, Rong

doi:10.1186/s12864-019-5510-y

Cited by 36 publications

(26 citation statements)

References 40 publications

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“…Gut microbiota disorder can be detected in a variety of non-gut systemic autoimmune disease, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and spondyloarthritis (SpA). A data-driven study suggested that gut microbiota and its metabolites contribute to RA at genetic, functional, and phenotypic levels (Wang & Xu, 2019). Animal models found a single commensal microbe can drive RA by promoting Th17 cells (Wu et al, 2010) or Tfh cells (Teng et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Effects of changes on gut microbiota in children with acute Kawasaki disease

Shen¹,

Ding²,

Yang³

et al. 2020

PeerJ

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Background Kawasaki disease (KD) is an acute febrile illness of early childhood. The exact etiology of the disease remains unknown. At present, research on KD is mostly limited to susceptibility genes, infections, and immunity. However, research on the correlation between gut microbiota and KD is rare. Methods Children with a diagnosis of acute KD and children undergoing physical examination during the same period were included. At the time of admission, the subjects’ peripheral venous blood and feces were collected. Faecal samples were analyzed for bacterial taxonomic content via high-throughput sequencing. The abundance, diversity, composition, and characteristic differences of the gut microbiota in KD and healthy children were compared by alpha diversity, beta diversity, linear discriminant analysis and LDA effect size analysis. Blood samples were used for routine blood examination, biochemical analysis, and immunoglobulin quantitative detection. Results Compared with the control group, the community richness and structure of gut microbiota in the KD group was significantly reduced (Chao1 richness estimator, mean 215.85 in KD vs. mean 725.76 in control, p < 0.01; Shannon diversity index, mean 3.32 in KD vs. mean 5.69 in control, p < 0.05). LEfSe analysis identified two strains of bacteria significantly associated with KD: Bacteroidetes and Dorea. Bacteroidetes were enriched in healthy children (mean 0.16 in KD vs. mean 0.34 in control, p < 0.05). Dorea was also enriched in healthy children but rarely existed in children with KD (mean 0.002 in KD vs. mean 0.016 in control, p < 0.05). Compared with the control, IgA and IgG in the KD group decreased (IgA, median 0.68 g/L in KD vs. median 1.06 g/L in control, p < 0.001; IgG, median 6.67 g/L in KD vs. median 9.71 g/L in control, p < 0.001), and IgE and IgM levels were not significantly changed. Conclusions Dysbiosis of gut microbiota occurs in children with acute KD and may be related to the etiology or pathogenesis of KD. It is worth noting that for the first time, we found that Dorea, a hydrogen-producing bacterium, was significantly reduced in children with acute KD. Overall, our results provide a theoretical basis for the prevention or diagnosis of KD based on intestinal microecology.

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Section: Discussionmentioning

confidence: 99%

Effects of changes on gut microbiota in children with acute Kawasaki disease

Shen¹,

Ding²,

Yang³

et al. 2020

PeerJ

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“…172 Microbiome-derived metabolites, most notably SCFAs, interact with a variety of immune pathways implicated in RA. 173 Spontaneous development of T cell-mediated autoimmune arthritis in IL1rn -/mice requires the activation of TLR2 and TLR4 by microbial ligands. 174 Dysbiotic microbiota from IL1rn -/mice elicits a IL17 response by intestinal lymphocytes.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Interaction between microbiota and immunity in health and disease

2020

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The interplay between the commensal microbiota and the mammalian immune system development and function includes multifold interactions in homeostasis and disease. The microbiome plays critical roles in the training and development of major components of the host's innate and adaptive immune system, while the immune system orchestrates the maintenance of key features of host-microbe symbiosis. In a genetically susceptible host, imbalances in microbiota-immunity interactions under defined environmental contexts are believed to contribute to the pathogenesis of a multitude of immune-mediated disorders. Here, we review features of microbiome-immunity crosstalk and their roles in health and disease, while providing examples of molecular mechanisms orchestrating these interactions in the intestine and extra-intestinal organs. We highlight aspects of the current knowledge, challenges and limitations in achieving causal understanding of host immune-microbiome interactions, as well as their impact on immune-mediated diseases, and discuss how these insights may translate towards future development of microbiometargeted therapeutic interventions.

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“…A number of studies have investigated chronic inflammatory disease-associated dysbiosis at various body sites using a range of molecular and biochemical approaches. RA has been associated with dysbiosis of the gastrointestinal tract (Taneja, 2014;Zhang et al, 2015;Chen et al, 2016;Liu et al, 2016;Horta-Baas et al, 2017;Wu et al, 2017;du Teil Espina et al, 2018;Picchianti-Diamanti et al, 2018;Wang and Xu, 2019), oral cavity (Zhang et al, 2015;Cheng et al, 2017;Beyer et al, 2018;Lopez-Oliva et al, 2018;Mikuls et al, 2018), lung (Scher et al, 2016b), and synovial fluid (Martinez-Martinez et al, 2009;Reichert et al, 2013;Zhao et al, 2018b) across a range of studies. Moreover, these studies have begun to associate RA, or stages thereof, with the presence or absence of specific bacteria, suggesting that the microbiome may afford a valuable source of novel biomarkers and or novel targets for therapeutic modulation (Brusca et al, 2014;Costello et al, 2015;Zhang et al, 2015;Cheng et al, 2017;Horta-Baas et al, 2017;Jethwa and Abraham, 2017;Wen et al, 2017).…”

Section: Rheumatoid Arthritis Ankylosing Spondylitis Psoriatic Arthmentioning

confidence: 99%

Molecular Characterization of Circulating Microbiome Signatures in Rheumatoid Arthritis

Hammad

Hider

Liyanapathirana

et al. 2020

Front. Cell. Infect. Microbiol.

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Rheumatoid Arthritis (RA) has been increasingly associated with perturbations to the microbial communities that reside in and on the body (the microbiome), in both human and animal studies. To date, such studies have mainly focused on the microbial communities that inhabit the gut and oral cavity. Mounting evidence suggests that microbial DNA can be detected in the blood circulation using a range of molecular methods. This DNA may represent an untapped pool of biomarkers that have the potential to report on changes to the microbiome of distant sites (e.g., example, the gut and oral cavity). To this end, through amplification and sequencing of the bacterial 16S rRNA variable region four, we evaluated the presence and identity of microbial DNA in blood samples obtained from RA patients (both prior to and 3 months following the instigation of treatment) in comparison to a small number of healthy control subjects and samples obtained from patients with ankylosing spondylitis (AS) and psoriatic arthritis (PA). Bacterial-derived DNA was identified in the majority of our patient samples. Taxonomic classification revealed that the microbiome community in RA was distinct from AS, PA, and the healthy state. Through analysis of paired patient samples obtained prior to and 3 months following treatment (V0 vs. V3), we found the microbiome to be modulated by treatment, and in many cases, this shift reduced the distance between these samples and the healthy control samples, suggesting a partial normalization following treatment in some patients. This effect was especially evident in seronegative arthritis patients. Herein, we provide further evidence for the existence of a blood microbiome in health and identify specific taxa modulated in disease and following treatment. These blood-derived signatures may have significant utility as disease biomarkers and suggest this area warrants further investigation.

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Data-driven multiple-level analysis of gut-microbiome-immune-joint interactions in rheumatoid arthritis

Cited by 36 publications

References 40 publications

Effects of changes on gut microbiota in children with acute Kawasaki disease

Effects of changes on gut microbiota in children with acute Kawasaki disease

Interaction between microbiota and immunity in health and disease

Molecular Characterization of Circulating Microbiome Signatures in Rheumatoid Arthritis

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