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      The Oral Microbiome in Treatment-Naïve Paediatric IBD Patients Exhibits Dysbiosis Related to Disease Severity that Resolves Following Therapy

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          Abstract

          Background

          There is a limited literature describing the oral microbiome and its diagnostic potential in paediatric inflammatory bowel disease [IBD].

          Methods

          We examined the dorsum tongue microbiome by V1–V2 sequencing in a cohort of 156 treatment-naïve children diagnosed with IBD compared to 102 healthy control children. Microbiome changes over time following treatment were examined in a subset of patients and associations between IBD diagnosis and dysbiosis were explored.

          Results

          Analysis of community structure of the microbiome in tongue samples revealed that IBD samples diverged significantly from healthy control samples [PERMANOVA p = 0.0009] and exhibited a reduced abundance of Clostridia in addition to several major oral genera [ Veillonella, Prevotella and Fusobacterium species] with an increased abundance of streptococci. This dysbiosis was more marked in patients with severe disease. Higher levels of the potential pathobionts Klebsiella and Pseudomonas spp. were also associated with IBD. In terms of predicted functions, the IBD oral microbiome was potentially more acidogenic and exhibited reduced capacity for B vitamin biosynthesis. We used a machine learning approach to develop a predictive model of IBD which exhibited a mean-prediction AUC [area under the ROC curve] of 0.762. Finally, we examined a subset of 53 patients following 12 months of therapy and could show resolution of oral dysbiosis as demonstrated by a shift towards a healthy community structure and a significant reduction in oral dysbiosis.

          Conclusion

          Oral dysbiosis found in children with IBD is related to disease severity and resolves over time following successful IBD treatment.

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          Most cited references51

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            DADA2: High resolution sample inference from Illumina amplicon data

            We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
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                Author and article information

                Contributors
                Journal
                J Crohns Colitis
                J Crohns Colitis
                eccojc
                Journal of Crohn's & Colitis
                Oxford University Press (UK )
                1873-9946
                1876-4479
                April 2023
                14 October 2022
                14 October 2022
                : 17
                : 4
                : 553-564
                Affiliations
                School of Dental Science, Trinity College Dublin and Dublin Dental University Hospital , Dublin 2, Republic of Ireland
                School of Dental Science, Trinity College Dublin and Dublin Dental University Hospital , Dublin 2, Republic of Ireland
                School of Dental Science, Trinity College Dublin and Dublin Dental University Hospital , Dublin 2, Republic of Ireland
                DOCHAS Study, Children’s Health Ireland, Crumlin, Dublin, Republic of Ireland
                DOCHAS Study, Children’s Health Ireland, Crumlin, Dublin, Republic of Ireland
                DOCHAS Study, Children’s Health Ireland, Crumlin, Dublin, Republic of Ireland
                Department of Paediatrics, University of Medicine and Health Sciences, RCSI, Dublin and University College Dublin , Ireland
                School of Dental Science, Trinity College Dublin and Dublin Dental University Hospital , Dublin 2, Republic of Ireland
                Author notes

                Hussey and Moran. Joint authors.

                Corresponding authors: Gary Moran, School of Dental Science, Trinity College Dublin and Dublin Dental University Hospital, Dublin 2, Republic of Ireland. Tel: +353-1-612-7245; Email: gpmoran@ 123456dental.tcd.ie ; Séamus Hussey, National Children’s Research Centre, Children’s Health Ireland (CHI), Crumlin, Dublin 12, Republic of Ireland. Tel: +353-1-409-6585; Email: seamus.hussey@ 123456ucd.ie
                Author information
                https://orcid.org/0000-0002-9362-0465
                https://orcid.org/0000-0003-0469-1788
                Article
                jjac155
                10.1093/ecco-jcc/jjac155
                10115232
                36239621
                3140887b-5da1-4be6-87aa-26baa2dcf338
                © The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 16 November 2022
                Page count
                Pages: 12
                Funding
                Funded by: Irish Health Research Board;
                Award ID: ILP-POR-2019-030
                Funded by: National Children’s Research Centre, Dublin;
                Award ID: J/15/1
                Award ID: C/18/2
                Categories
                Original Articles
                Eccojc/1140
                AcademicSubjects/MED00260

                oral microbiome,paediatric,ibd,dysbiosis
                oral microbiome, paediatric, ibd, dysbiosis

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