Early Life Antibiotics Influence In Vivo and In Vitro Mouse Intestinal Epithelium Maturation and FunctioningSummary
| Autor: | Jan Koster, Pim J. Koelink, Manon van Roest, Sander Meisner, Ingrid B. Renes, William J. Faller, Joana Silva, Wouter L. Smit, Jacqueline L.M. Vermeulen, Manon E. Wildenberg, Vanesa Muncan, Ruurd M. van Elburg, Tânia Martins Garcia |
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| Přispěvatelé: | Tytgat Institute for Liver and Intestinal Research, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Graduate School, Oncogenomics, AII - Inflammatory diseases, ARD - Amsterdam Reproduction and Development |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
ACS apical canalicular system Antibiotics RC799-869 IEC intestinal epithelial cell Mice 0302 clinical medicine GSEA gene set enrichment analysis EEC enteroendocrine cell Gene expression Gene Regulatory Networks OCR oxygen consumption rate Oligonucleotide Array Sequence Analysis Original Research Ass1 argininosuccinate synthase 1 P postnatal day GIP gastric inhibitory polypeptide Gastroenterology AB antibiotics Diseases of the digestive system. Gastroenterology Intestinal epithelium Anti-Bacterial Agents Intestines EpCAM epithelial cell adhesion molecule 030211 gastroenterology & hepatology FITC fluorescein isothiocyanate Arg2 arginase 2 Antibiotic Treatment Postnatal Care ATP adenosine triphosphate medicine.drug_class PBS phosphate-buffered saline FCCP carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone Biology Permeability Andrology 03 medical and health sciences SI small intestine In vivo Vancomycin Metronidazole GO Gene Ontology medicine Organoid Animals Fetus NEC necrotizing enterocolitis Intestinal permeability ECAR extracellular acidification rate Hepatology Gene Expression Profiling Fetal Organoids Amoxicillin medicine.disease In vitro qRT-PCR quantitative reverse-transcription polymerase chain reaction 2-DG 2-deoxy-glucose Neonatal Intestine Disease Models Animal Sis sucrase-isomaltase 030104 developmental biology Enterocytes Animals Newborn Gene Expression Regulation Vacuoles |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 3, Pp 943-981 (2021) Cellular and Molecular Gastroenterology and Hepatology Cellular and molecular gastroenterology and hepatology, 12(3), 943-981. Elsevier Inc. |
| ISSN: | 2352-345X |
| Popis: | Background & Aims The use of antibiotics (ABs) is a common practice during the first months of life. ABs can perturb the intestinal microbiota, indirectly influencing the intestinal epithelial cells (IECs), but can also directly affect IECs independent of the microbiota. Previous studies have focused mostly on the impact of AB treatment during adulthood. However, the difference between the adult and neonatal intestine warrants careful investigation of AB effects in early life. Methods Neonatal mice were treated with a combination of amoxicillin, vancomycin, and metronidazole from postnatal day 10 to 20. Intestinal permeability and whole-intestine gene and protein expression were analyzed. IECs were sorted by a fluorescence-activated cell sorter and their genome-wide gene expression was analyzed. Mouse fetal intestinal organoids were treated with the same AB combination and their gene and protein expression and metabolic capacity were determined. Results We found that in vivo treatment of neonatal mice led to decreased intestinal permeability and a reduced number of specialized vacuolated cells, characteristic of the neonatal period and necessary for absorption of milk macromolecules. In addition, the expression of genes typically present in the neonatal intestinal epithelium was lower, whereas the adult gene expression signature was higher. Moreover, we found altered epithelial defense and transepithelial-sensing capacity. In vitro treatment of intestinal fetal organoids with AB showed that part of the consequences observed in vivo is a result of the direct action of the ABs on IECs. Lastly, ABs reduced the metabolic capacity of intestinal fetal organoids. Conclusions Our results show that early life AB treatment induces direct and indirect effects on IECs, influencing their maturation and functioning. Graphical abstract |
| Databáze: | OpenAIRE |
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