PXD007914-1

PXD007914 is an original dataset announced via ProteomeXchange.

Title	Mouse stool samples in response to antibiotic treatment
Description	Background and Objectives: Antibiotic (ABx) therapy is associated with an increased risk for Crohn´s Disease but the underlying mechanisms are unknown. We observed high fecal serine protease activity (PA) to be a frequent side effect of ABx therapy in patients. The aim of the present study was to unravel whether this rise in PA may promote colitis development via detrimental effects on the large intestinal barrier. Design: Transwell experiments were used to assess the impact of high PA in ABx-treated patients or vancomycin/metronidazole (V/M)-treated mice on the epithelial barrier. Serine protease profiling was performed using LC-MS/MS analysis. The impact of high PA on the intestinal barrier in WT/IL10-/- mice and on colitis development in IL10-/- mice was investigated using V/M+/-oral serine protease inhibitor (AEBSF) treatment. Results: The ABx-induced high PA was found to be due to significantly increased levels of pancreatic proteases and to impair the epithelial barrier. In WT mice, the rise in PA caused a transient increase in intestinal permeability but did not affect susceptibility towards DSS-induced acute colitis. In IL10-/- mice, the rise in PA caused a lasting impairment of the intestinal barrier, which was associated with inflammatory activation of the large intestinal tissue. In the long term, the lasting increase in PA upon repeated V/M treatment aggravated colitis development in IL10-/-mice. Conclusion: High 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 inflammation in genetically susceptible individuals.
HostingRepository	PRIDE
AnnounceDate	2018-05-11
AnnouncementXML	Submission_2018-05-11_08:15:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Ludwig
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-09 01:55:57	ID requested
⏵ 1	2018-05-11 08:15:11	announced

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: mouse, stool, antibiotic treatment, protease activity, intestinal barrier, Velos

Christina Ludwig
contact affiliation	Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Technische Universität München, Freising-Weihenstephan, Germany
contact email	tina.ludwig@tum.de
lab head
Christina Ludwig
contact affiliation	TU Munich
contact email	tina.ludwig@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007914
     1. Label: PRIDE project
     2. Name: Mouse stool samples in response to antibiotic treatment