Targeted Metabolomics Analysis Identifies Intestinal Microbiota-Derived Urinary Biomarkers of Colonization Resistance in Antibiotic-Treated Mice
Autor: | Steven N. Emancipator, Mark E. Obrenovich, Alex Polinkovsky, Curtis J. Donskey, Renliang Zhang, Mary Ann Tima |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.drug_class Urinary system 030106 microbiology Antibiotics Glycine Penicillanic Acid Urine Aztreonam Colonisation resistance Biology Bioinformatics Lignans Microbiology 03 medical and health sciences chemistry.chemical_compound Mice In vivo Mechanisms of Resistance Tandem Mass Spectrometry Drug Resistance Bacterial medicine polycyclic compounds Animals Metabolomics Pharmacology (medical) Enterodiol Pharmacology Piperacillin Clostridioides difficile Tryptophan Anti-Bacterial Agents Gastrointestinal Microbiome Intestines 030104 developmental biology Infectious Diseases Tryptophan Metabolite Piperacillin Tazobactam Drug Combination chemistry Metabolome Biomarkers Chromatography Liquid |
Popis: | Antibiotics excreted into the intestinal tract may disrupt the microbiota that provide colonization resistance against enteric pathogens and alter normal metabolic functions of the microbiota. Many of the bacterial metabolites produced in the intestinal tract are absorbed systemically and excreted in urine. Here, we used a mouse model to test the hypothesis that alterations in levels of targeted bacterial metabolites in urine specimens could provide useful biomarkers indicating disrupted or intact colonization resistance. To assess in vivo colonization resistance, mice were challenged with Clostridium difficile spores orally 3, 6, and 11 days after the completion of 2 days of treatment with piperacillin-tazobactam, aztreonam, or saline. For concurrent groups of antibiotic-treated mice, urine samples were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify the concentrations of 11 compounds targeted as potential biomarkers of colonization resistance. Aztreonam did not affect colonization resistance, whereas piperacillin-tazobactam disrupted colonization resistance 3 days after piperacillin-tazobactam treatment, with complete recovery by 11 days after treatment. Three of the 11 compounds exhibited a statistically significant and >10-fold increase (the tryptophan metabolite N -acetyltryptophan) or decrease (the plant polyphenyl derivatives cinnamoylglycine and enterodiol) in concentrations in urine 3 days after piperacillin-tazobactam treatment, followed by recovery to baseline that coincided with the restoration of in vivo colonization resistance. These urinary metabolites could provide useful and easily accessible biomarkers indicating intact or disrupted colonization resistance during and after antibiotic treatment. |
Databáze: | OpenAIRE |
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