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Early Life Antibiotics Influence In Vivo and In Vitro Mouse Intestinal Epithelium Maturation and FunctioningSummary
- Source :
- 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.
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- 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.<br />Graphical abstract
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 2352345X
- Volume :
- 12
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Gastroenterology and Hepatology
- Accession number :
- edsair.doi.dedup.....4c861cf76325ee471195673d49383545