‘All disease begins in the gut’—the role of the intestinal microbiome in ankylosing spondylitis

Harkins, Patricia; Burke, Eoghan; Swales, Catherine; Silman, Alan J.

doi:10.1093/rap/rkab063

Cited by 10 publications

(7 citation statements)

References 101 publications

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“…Prevotella is associated with dysbiosis and the pathogenesis of arthritis. Studies in patients with AS have shown that Prevotella could be increased or decreased in the gut microbiota; however, its pro-inflammatory potential is widely recognized [ 40 , 41 ]. Moreover, in HLA-B27-positive transgenic rats, Prevotella dysregulates the key pathogenic cytokines, including IL-17, IL-23, and TNF-α [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process

González-Chávez

Salas‐Leiva

et al. 2023

PLoS ONE

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To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice’s stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice’s stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies.

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Section: Discussionmentioning

confidence: 99%

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process

González-Chávez

Salas‐Leiva

et al. 2023

PLoS ONE

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“…In general, loss of the overall diversity, loss of commensal, beneficial organisms or excessive growth of potentially harmful ones, pathobionts, aspects not mutually exclusive, are criteria for diagnosing dysbiosis, a key term in the human microbiome field especially used to mediate the association of microbiome patterns to disease states that need to imply a fine-grained analysis (33,34). Several studies focusing on the intestinal microbiome and how it relates to AS disease revealed alterations in the gut microbiome in patients with AS, but, to date, no distinct AS microbial signature has been identified (35). In spite of the tendency of greater pooled diversity of the HC group than of the AS group which further needs more refined consideration as some of the low abundant or not uniform across the cohort taxa may be a potential source of beneficial or pathogenic organisms, we have limited evidence of a significant difference between the gut microbiomes as a whole in AS patients and healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

An insight into the fecal microbiota composition in Romanian patients with ankylosing spondylitis using high-throughput 16S rRNA gene amplicon sequencing

Oprea¹,

Cristea²,

Dinu³

et al. 2022

Revista Romana De Medicina De Laborator

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Introduction. Application of next-generation sequencing technology generated a massive amount of information on the gut microbiome composition used to understand its role in the healthy state and in various diseases. We aimed to provide information on the gut microbiota composition of Romanian subjects diagnosed with ankylosing spondylitis, an immune-mediated arthropathy linked to a genetic predisposition and gut dysbiosis. Methods. Stool samples collected from 25 patients with ankylosing spondylitis and 16 healthy controls were investigated using high-throughput DNA sequencing of 16S rRNA amplicons from seven different hypervariable regions and Ion Torrent PGM instrument. Microbial composition of metagenomic data was analyzed with QIIME software and differential abundance analysis of taxa encompassed linear discriminant analysis effect size (LEfSe). Results. Overall, 14 phyla, 114 families, 114 genera, and 275 species were identified across the 41 samples, the aggregated data revealing as most abundant the phyla Bacteroidetes, Firmicutes, and Proteobacteria, the families Bacteroidaceae, Prevotellaceae, and Ruminococcaceae, the genera Bacteroides, Prevotella, and Faecalibacterium, and Prevotella copri species. Using various cutoffs for abundance and prevalence, core taxonomic members were identified which in general were shared between the patients and controls. However, evidence was gained that the diversity in the microbiomes from the former cohort was lower than for controls and that certain taxa had significantly different abundance between the two groups. Conclusion. This study allowed an informative high-throughput 16S rRNA profiling of the gut microbiota needed to identify microbiome signatures of risk in the autochthonous population with AS.

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“…Secondly, establishing causation as opposed to association remains problematic [36]. Thirdly, there is the challenge of establishing whether there exists a characteristic microbiome that is specific to AS patients (Figure 3) [40]. Many of these microbes were thought to be gut commensals, but new studies have shown them to be increased specifically with disease and thus are regarded as pathobiont [36].…”

Section: Infections and Microbiomementioning

confidence: 99%

Ankylosing Spondylitis Pathogenesis and Pathophysiology

Alexander¹

2023

Ankylosing Spondylitis - Recent Concepts

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The pathogenesis and pathophysiology of Ankylosing Spondylitis (AS) is complex and remains only partially understood. Contributory genes including a variety of HLA-B27 subset genes and many other non-HLA genes are implicated in the literature. Novel genes and gene–gene interactions being a continuously evolving area of AS research. Dysregulation of the enteric microbiome with a corresponding aberrant immunological response is recognised in research. Certain infectious agents are thought to play a role. A variety of other influences including environmental exposures, dietary and lifestyle factors and sex hormones appear to play a role in AS pathogenesis. There is emerging evidence that that pathophysiological response in AS is an elaborate combination of both autoinflammatory and autoimmune components, however the IL-17/IL-23 pathway remains the major pathway in AS according to studies to date. The specific mechanisms that lead to characteristic clinical features of AS including sacroiliitis, spondylitis, ankylosis, uveitis and other extra articular manifestations remain occult. Further research to establish these is ongoing.

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‘All disease begins in the gut’—the role of the intestinal microbiome in ankylosing spondylitis

Cited by 10 publications

References 101 publications

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process

An insight into the fecal microbiota composition in Romanian patients with ankylosing spondylitis using high-throughput 16S rRNA gene amplicon sequencing

Ankylosing Spondylitis Pathogenesis and Pathophysiology

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