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The Relationship Between Mucosal Microbiota, Colitis, and Systemic Inflammation in Chronic Granulomatous Disorder

Davrandi, M; Harris, S; Smith, PJ; Murray, CD; Lowe, DM; (2021) The Relationship Between Mucosal Microbiota, Colitis, and Systemic Inflammation in Chronic Granulomatous Disorder. Journal of Clinical Immunology 10.1007/s10875-021-01165-6. (In press).

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Lowe_The Relationship Between Mucosal Microbiota, Colitis, and Systemic Inflammation in Chronic Granulomatous Disorder_AAM.pdf - Accepted Version
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Abstract

PURPOSE: Chronic granulomatous disorder (CGD) is a primary immunodeficiency which is frequently complicated by inflammatory colitis and is associated with systemic inflammation. Herein, we aimed to investigate the role of the microbiome in the pathogenesis of colitis and systemic inflammation. METHODS: We performed 16S rDNA sequencing on mucosal biopsy samples from each segment of 10 CGD patients’ colons and conducted compositional and functional pathway prediction analyses. RESULTS: The microbiota in samples from colitis patients demonstrated reduced taxonomic alpha-diversity compared to unaffected patients, even in apparently normal bowel segments. Functional pathway richness was similar between the colitic and non-colitic mucosa, although metabolic pathways involved in butyrate biosynthesis or utilization were enriched in patients with colitis and correlated positively with fecal calprotectin levels. One patient with very severe colitis was dominated by Enterococcus spp., while among other patients Bacteroides spp. abundance correlated with colitis severity measured by fecal calprotectin and an endoscopic severity score. In contrast, Blautia abundance is associated with low severity scores and mucosal health. Several taxa and functional pathways correlated with concentrations of inflammatory cytokines in blood but not with colitis severity. Notably, dividing patients into “high” and “low” systemic inflammation groups demonstrated clearer separation than on the basis of colitis status in beta-diversity analyses. CONCLUSION: The microbiome is abnormal in CGD-associated colitis and altered functional characteristics probably contribute to pathogenesis. Furthermore, the relationship between the mucosal microbiome and systemic inflammation, independent of colitis status, implies that the microbiome in CGD can influence the inflammatory phenotype of the condition.

Type: Article
Title: The Relationship Between Mucosal Microbiota, Colitis, and Systemic Inflammation in Chronic Granulomatous Disorder
DOI: 10.1007/s10875-021-01165-6
Publisher version: https://doi.org/10.1007/s10875-021-01165-6
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: CGD, Chronic granulomatous disorder, Colitis, Microbiome, Bacteroides, Blautia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10138865
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