Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota

Regner, Emilie; Ohri, Neha; Stahly, Andrew; Gerich, Mark E.; Fennimore, Blair; Ir, Diana; Jubair, Widian; Görg, Carsten; Siebert, Janet; Robertson, Charles E.; Caplan, Liron; Frank, Daniel N.; Kuhn, Kristine A.

doi:10.1186/s13075-018-1639-3

Cited by 45 publications

(35 citation statements)

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“…Furthermore, IELs regulate epithelial barrier integrity as they are the primary sensors of microbial antigens presented by epithelial cells and lamina propria macrophages 131,132 . A 2018 study suggested a decrease in IEL number in patients with axSpA compared with healthy individuals, but not in patients with Crohn's disease or ulcerative colitis 133 . In this study, IELs from patients with Crohn's disease and those with axSpA were found to produce increased levels of TNF, but only IELs from patients with Crohn's disease produced more IL-17 than healthy individuals.…”

Section: Immunological Alterations In Spamentioning

confidence: 99%

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

et al. 2020

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Gut inflammation is strongly associated with spondyloarthritis (SpA), as exemplified by the high prevalence of inflammatory bowel disease (IBD) and the even higher occurrence of subclinical gut inflammation in patients with SpA. The gut-joint axis of inflammation in SpA is further reinforced by similarities in immunopathogenesis at both anatomical sites and by the clinical success of therapies blocking TNF and IL-23 in IBD and in some forms of SpA. Many genetic risk factors are shared between SpA and IBD, and changes in the composition of gut microbiota are seen in both diseases. Current dogma is that inflammation in SpA initiates in the gut and leads to joint inflammation; however, although conceptually attractive, some research does not support this causal relationship. For example, therapies targeting IL-17A are efficacious in the joint but not the gut, and interfering with gut trafficking by targeting molecules such as α4β7 in IBD can lead to onset or flares of SpA. Several important knowledge gaps remain that must be addressed in future studies. Determining the true nature of the gut-joint axis has real-world implications for the treatment of patients with co-incident IBD and SpA and for the repurposing of therapeutics from one disease to the other.

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Section: Immunological Alterations In Spamentioning

confidence: 99%

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

et al. 2020

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“…The first case study interrogates microbiome:cytokine relationships in fecal samples from HIV-negative high risk individuals and HIV-negative low risk individuals. The second case study uses published data, and identifies new findings in fecal microbiome:cytokine relationships in patients with spondyloarthritis, Crohn’s disease, ulcerative colitis, and healthy controls [30]. The third case study considers microbiome:immune cell relationships in gut biopsies in HIV-positive and HIV-negative participants.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, Regner et al reported on relationships between the gut microbiome and cytokines produced by mitogen-stimulated intraepithelial lymphocytes (IEL) in patients with spondyloarthritis (SpA), Crohn’s disease (CD), ulcerative colitis (UC), and healthy controls (HC) [30]. Among other results, Regner identified elevated levels of TNFα in patients with SpA and CD.…”

Section: Resultsmentioning

confidence: 99%

VOLARE: visual analysis of disease-associated microbiome-immune system interplay

et al. 2019

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Background: Relationships between specific microbes and proper immune system development, composition, and function have been reported in a number of studies. However, researchers have discovered only a fraction of the likely relationships. "Omic" methodologies such as 16S ribosomal RNA (rRNA) sequencing and time-of-flight mass cytometry (CyTOF) immunophenotyping generate data that support generation of hypotheses, with the potential to identify additional relationships at a level of granularity ripe for further experimentation. Pairwise linear regressions between microbial and host immune features provide one approach for quantifying relationships between "omes", and the differences in these relationships across study cohorts or arms. This approach yields a top table of candidate results. However, the top table alone lacks the detail that domain experts such as microbiologists and immunologists need to vet candidate results for follow-up experiments. Results: To support this vetting, we developed VOLARE (Visualization Of LineAr Regression Elements), a web application that integrates a searchable top table, small in-line graphs illustrating the fitted models, a network summarizing the top table, and on-demand detailed regression plots showing full sample-level detail. We applied VOLARE to three case studies-microbiome:cytokine data from fecal samples in human immunodeficiency virus (HIV), microbiome:cytokine data in inflammatory bowel disease and spondyloarthritis, and microbiome:immune cell data from gut biopsies in HIV. We present both patient-specific phenomena and relationships that differ by disease state. We also analyzed interaction data from system logs to characterize usage scenarios. This log analysis revealed that users frequently generated detailed regression plots, suggesting that this detail aids the vetting of results. Conclusions: Systematically integrating microbe:immune cell readouts through pairwise linear regressions and presenting the top table in an interactive environment supports the vetting of results for scientific relevance. VOLARE allows domain experts to control the analysis of their results, screening dozens of candidate relationships with ease. This interactive environment transcends the limitations of a static top table.

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“…The first case study interrogates microbiome:cytokine relationships in fecal samples from HIV-negative high risk individuals and HIVnegative low risk individuals. The second case study uses published data, and identifies new findings in fecal microbiome:cytokine relationships in patients with spondyloarthritis, Crohn's disease, ulcerative colitis, and healthy controls (29). The third case study considers microbiome:immune cell relationships in gut biopsies in HIV-positive and HIV-negative participants.…”

Section: Resultsmentioning

confidence: 99%

VOLARE: Visual analysis of disease-associated microbiome-immune system interplay

Siebert

Neff

Schneider

et al. 2018

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BackgroundRelationships between specific microbes and proper immune system development, composition, and function have been reported in a number of studies. However, researchers have discovered only a fraction of the likely relationships. High-dimensional “omic” methodologies such as 16S ribosomal RNA (rRNA) sequencing and Time-of-flight mass cytometry (CyTOF) immunophenotyping generate data that support generation of hypotheses, with the potential to identify additional relationships at a level of granularity ripe for further experimentation. Pairwise linear regressions between microbial and host immune features is one approach for quantifying relationships between “omes”, and the differences in these relationships across study cohorts or arms. This approach yields a top table of candidate results. However, the top table alone lacks the detail that domain experts need to vet candidate results for follow-up experiments.ResultsTo support this vetting, we developed VOLARE (Visualization Of LineAr Regression Elements), a web application that integrates a searchable top table, small in-line graphs illustrating the fitted models, a network summarizing the top table, and on-demand detailed regression plots showing full sample-level detail. We applied VOLARE to three case studies—microbiome:cytokine data from fecal samples in HIV, microbiome:cytokine data in inflammatory bowel disease and spondyloarthritis, and microbiome:immune cell data from gut biopsies in HIV. We present both patient-specific phenomena and relationships that differ by disease state. We also analyzed interaction data from system logs to characterize usage scenarios. This log analysis revealed that, in using VOLARE, domain experts frequently generated detailed regression plots, suggesting that this detail aids the vetting of results.ConclusionsSystematically integrating microbe:immune cell readouts through pairwise linear regressions and presenting the top table in an interactive environment supports the vetting of results for scientific relevance. VOLARE allows domain experts to control the analysis of their results, screening dozens of candidate relationships with ease. This interactive environment transcends the limitations of a static top table.

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Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota

Cited by 45 publications

References 46 publications

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

VOLARE: visual analysis of disease-associated microbiome-immune system interplay

VOLARE: Visual analysis of disease-associated microbiome-immune system interplay

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