Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummary
Background & Aims: Antibiotic (ABx) therapy is associated with increased risk for Crohn’s disease but underlying mechanisms are unknown. We observed high fecal serine protease activity (PA) to be a frequent side effect of ABx therapy. The aim of the present study was to unravel whether this rise...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-01-01
|
| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X18300845 |
| id |
doaj-8bdaa6a4d60142b0a6fe9d1d92e59fbf |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Hongsup Yoon Monika Schaubeck Ilias Lagkouvardos Andreas Blesl Stephanie Heinzlmeir Hannes Hahne Thomas Clavel Suchita Panda Christina Ludwig Bernhard Kuster Chaysavanh Manichanh Patrizia Kump Dirk Haller Gabriele Hörmannsperger |
| spellingShingle |
Hongsup Yoon Monika Schaubeck Ilias Lagkouvardos Andreas Blesl Stephanie Heinzlmeir Hannes Hahne Thomas Clavel Suchita Panda Christina Ludwig Bernhard Kuster Chaysavanh Manichanh Patrizia Kump Dirk Haller Gabriele Hörmannsperger Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummary Cellular and Molecular Gastroenterology and Hepatology |
| author_facet |
Hongsup Yoon Monika Schaubeck Ilias Lagkouvardos Andreas Blesl Stephanie Heinzlmeir Hannes Hahne Thomas Clavel Suchita Panda Christina Ludwig Bernhard Kuster Chaysavanh Manichanh Patrizia Kump Dirk Haller Gabriele Hörmannsperger |
| author_sort |
Hongsup Yoon |
| title |
Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummary |
| title_short |
Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummary |
| title_full |
Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummary |
| title_fullStr |
Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummary |
| title_full_unstemmed |
Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummary |
| title_sort |
increased pancreatic protease activity in response to antibiotics impairs gut barrier and triggers colitissummary |
| publisher |
Elsevier |
| series |
Cellular and Molecular Gastroenterology and Hepatology |
| issn |
2352-345X |
| publishDate |
2018-01-01 |
| description |
Background & Aims: Antibiotic (ABx) therapy is associated with increased risk for Crohn’s disease but underlying mechanisms are unknown. We observed high fecal serine protease activity (PA) to be a frequent side effect of ABx therapy. The aim of the present study was to unravel whether this rise in large intestinal PA may promote colitis development via detrimental effects on the large intestinal barrier. Methods: Transwell experiments were used to assess the impact of high PA in ABx-treated patients or vancomycin/metronidazole-treated mice on the epithelial barrier. Serine protease profiling was performed using liquid chromatography–mass spectrometry/mass spectrometry analysis. The impact of high large intestinal PA on the intestinal barrier in wild-type and interleukin (IL)10-/- mice and on colitis development in IL10-/- mice was investigated using vancomycin/metronidazole with or without oral serine protease inhibitor (AEBSF) treatment. Results: The ABx-induced, high large intestinal PA was caused by significantly increased levels of pancreatic proteases and impaired epithelial barrier integrity. In wild-type mice, the rise in PA caused a transient increase in intestinal permeability but did not affect susceptibility to chemically induced acute colitis. In IL10-/- mice, increased PA caused a consistent impairment of the intestinal barrier associated with inflammatory activation in the large intestinal tissue. In the long term, the vancomycin/metronidazole-induced lasting increase in PA aggravated colitis development in IL10-/- mice. Conclusions: High large intestinal PA is a frequent adverse effect of ABx therapy, which is detrimental to the large intestinal barrier and may contribute to the development of chronic intestinal inflammation in susceptible individuals. Keywords: Epithelial Barrier, Serine Proteases, Gut Microbiota, Inflammatory Bowel Diseases |
| url |
http://www.sciencedirect.com/science/article/pii/S2352345X18300845 |
| work_keys_str_mv |
AT hongsupyoon increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT monikaschaubeck increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT iliaslagkouvardos increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT andreasblesl increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT stephanieheinzlmeir increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT hanneshahne increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT thomasclavel increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT suchitapanda increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT christinaludwig increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT bernhardkuster increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT chaysavanhmanichanh increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT patriziakump increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT dirkhaller increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary AT gabrielehormannsperger increasedpancreaticproteaseactivityinresponsetoantibioticsimpairsgutbarrierandtriggerscolitissummary |
| _version_ |
1725958701908492288 |
| spelling |
doaj-8bdaa6a4d60142b0a6fe9d1d92e59fbf2020-11-24T21:32:05ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2018-01-0163370388.e3Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers ColitisSummaryHongsup Yoon0Monika Schaubeck1Ilias Lagkouvardos2Andreas Blesl3Stephanie Heinzlmeir4Hannes Hahne5Thomas Clavel6Suchita Panda7Christina Ludwig8Bernhard Kuster9Chaysavanh Manichanh10Patrizia Kump11Dirk Haller12Gabriele Hörmannsperger13Technische Universität München, Chair of Nutrition and Immunology, Freising-Weihenstephan, GermanyMax Planck Institute of Neurobiology, Department of Neuroimmunology, Martinsried, GermanyTechnische Universität München, Junior Research Group Microbial Bioinformatics, ZIEL – Institute for Food and Health, Freising-Weihenstephan, Germany; Technische Universität München, ZIEL – Institute for Food & Health, Freising-Weihenstephan, GermanyDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaTechnische Universität München, Chair of Proteomics and Bioanalytics, Freising-Weihenstephan, Germany; Technische Universität München, Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Freising-Weihenstephan, GermanyTechnische Universität München, Chair of Proteomics and Bioanalytics, Freising-Weihenstephan, Germany; OmicScouts GmbH, Freising, GermanyTechnische Universität München, ZIEL – Institute for Food & Health, Freising-Weihenstephan, Germany; RWTH University Hospital, Institute of Medical Microbiology, Functional Microbiome Research Group, Aachen, GermanyVall d'Hebron Research Institute, Digestive Research Unit, Barcelona, SpainTechnische Universität München, Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Freising-Weihenstephan, GermanyTechnische Universität München, Chair of Proteomics and Bioanalytics, Freising-Weihenstephan, Germany; Technische Universität München, Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Freising-Weihenstephan, GermanyVall d'Hebron Research Institute, Digestive Research Unit, Barcelona, SpainDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaTechnische Universität München, Chair of Nutrition and Immunology, Freising-Weihenstephan, Germany; Technische Universität München, ZIEL – Institute for Food & Health, Freising-Weihenstephan, Germany; Correspondence Address correspondence to: Dirk Haller, PhD, Chair of Nutrition and Immunology, Gregor-Mendel-Str.2, 85350 Freising-Weihenstephan, Germany.Technische Universität München, Chair of Nutrition and Immunology, Freising-Weihenstephan, Germany; Gabriele Hörmannsperger, PhD, Chair of Nutrition and Immunology, Gregor-Mendel-Str.2, 85350 Freising-Weihenstephan, Germany.Background & Aims: Antibiotic (ABx) therapy is associated with increased risk for Crohn’s disease but underlying mechanisms are unknown. We observed high fecal serine protease activity (PA) to be a frequent side effect of ABx therapy. The aim of the present study was to unravel whether this rise in large intestinal PA may promote colitis development via detrimental effects on the large intestinal barrier. Methods: Transwell experiments were used to assess the impact of high PA in ABx-treated patients or vancomycin/metronidazole-treated mice on the epithelial barrier. Serine protease profiling was performed using liquid chromatography–mass spectrometry/mass spectrometry analysis. The impact of high large intestinal PA on the intestinal barrier in wild-type and interleukin (IL)10-/- mice and on colitis development in IL10-/- mice was investigated using vancomycin/metronidazole with or without oral serine protease inhibitor (AEBSF) treatment. Results: The ABx-induced, high large intestinal PA was caused by significantly increased levels of pancreatic proteases and impaired epithelial barrier integrity. In wild-type mice, the rise in PA caused a transient increase in intestinal permeability but did not affect susceptibility to chemically induced acute colitis. In IL10-/- mice, increased PA caused a consistent impairment of the intestinal barrier associated with inflammatory activation in the large intestinal tissue. In the long term, the vancomycin/metronidazole-induced lasting increase in PA aggravated colitis development in IL10-/- mice. Conclusions: High large intestinal PA is a frequent adverse effect of ABx therapy, which is detrimental to the large intestinal barrier and may contribute to the development of chronic intestinal inflammation in susceptible individuals. Keywords: Epithelial Barrier, Serine Proteases, Gut Microbiota, Inflammatory Bowel Diseaseshttp://www.sciencedirect.com/science/article/pii/S2352345X18300845 |