Acute Experimental Barrier Injury Triggers Ulcerative Colitis–Specific Innate Hyperresponsiveness and Ulcerative Colitis–Type Microbiome Changes in Humans
| Autor: | Jakob Benedict Seidelin, Jens Vilstrup Johansen, Marina Ramírez Galera, Lene Riis, Tine Rask Licht, Benjamin E. Mead, Anders Woetmann, Martin Iain Bahl, Jeffrey M. Karp, Jacob Tveiten Bjerrum |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine DAMP damage-associated molecular pattern ILC3 RC799-869 Flare Initiation 0302 clinical medicine AMP antimicrobial peptide Intestinal Mucosa Original Research IBD inflammatory bowel disease Gastroenterology Sigmoid colon ILC innate lymphoid cell Middle Aged Diseases of the digestive system. Gastroenterology Control subjects Immunohistochemistry Ulcerative colitis rRNA ribosomal RNA medicine.anatomical_structure MES Mayo endoscopic subscore Disease Progression Innate Lymphoid Cells Type 3 qPCR quantitative polymerase chain reaction Cytokines Female 030211 gastroenterology & hepatology Disease Susceptibility Injury model Inflammation Mediators medicine.symptom Acute Mucosal Injury PAMP pathogen-associated molecular pattern Adult Innate Intestinal Response Inflammation 03 medical and health sciences GO Gene Ontology CD Crohn’s disease medicine Humans Ulcerative Colitis Microbiome Aged Host Microbial Interactions Hepatology business.industry Endoscopy NCR natural cytotoxicity receptor medicine.disease Immunity Innate Lymphocyte Subsets IL interleukin Gastrointestinal Microbiome UC ulcerative colitis 030104 developmental biology Case-Control Studies Immunology Dysbiosis Colitis Ulcerative business Biomarkers |
| Zdroj: | Seidelin, J B, Bahl, M I, Licht, T R, Mead, B E, Karp, J M, Johansen, J V, Riis, L B, Galera, M R, Woetmann, A & Bjerrum, J T 2021, ' Acute Experimental Barrier Injury Triggers Ulcerative Colitis–Specific Innate Hyperresponsiveness and Ulcerative Colitis–Type Microbiome Changes in Humans ', Cellular and Molecular Gastroenterology and Hepatology, vol. 12, no. 4, pp. 1281-1296 . https://doi.org/10.1016/j.jcmgh.2021.06.002 Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 4, Pp 1281-1296 (2021) Cellular and Molecular Gastroenterology and Hepatology |
| ISSN: | 2352-345X |
| DOI: | 10.1016/j.jcmgh.2021.06.002 |
| Popis: | Background and aims The trigger hypothesis opens the possibility of anti-flare initiation therapies by stating that ulcerative colitis (UC) flares originate from inadequate responses to acute mucosal injuries. However, experimental evidence is restricted by a limited use of suitable human models. We thus aimed to investigate the acute mucosal barrier injury responses in humans with and without UC using an experimental injury model. Methods A standardized mucosal break was inflicted in the sigmoid colon of 19 patients with UC in endoscopic and histological remission and 20 control subjects. Postinjury responses were assessed repeatedly by high-resolution imaging and sampling to perform Geboes scoring, RNA sequencing, and injury niche microbiota 16S ribosomal RNA gene sequencing. Results UC patients had more severe endoscopic postinjury inflammation than did control subjects (P < .01), an elevated modified Geboes score (P < .05), a rapid induction of innate response gene sets (P < .05) and antimicrobial peptides (P < .01), and engagement of neutrophils (P < .01). Innate lymphoid cell type 3 (ILC3) markers were increased preinjury (P < .01), and ILC3 activating cytokines were highly induced postinjury, resulting in an increase in ILC3-type cytokine interleukin-17A. Across groups, the postinjury mucosal microbiome had higher bacterial load (P < .0001) and lower α-diversity (P < .05). Conclusions UC patients in remission respond to mucosal breaks by an innate hyperresponse engaging resident regulatory ILC3s and a subsequent adaptive activation. The postinjury inflammatory bowel disease–like microbiota diversity decrease is irrespective of diagnosis, suggesting that the dysbiosis is secondary to host injury responses. We provide a model for the study of flare initiation in the search for antitrigger-directed therapies. Graphical abstract |
| Databáze: | OpenAIRE |
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