Abstract
The association between prolonged antibiotic (AB) use in neonates and increased incidence of later life diseases is not yet fully understood. AB treatment in early life alters intestinal epithelial cell composition, functioning, and maturation, which could be the basis for later life health effects. Here, we investigated whether AB-induced changes in the neonatal gut persisted up to adulthood and whether early life AB had additional long-term consequences for gut functioning. Mice received AB orally from postnatal day 10 to 20. Intestinal morphology, permeability, and gene and protein expression at 8 weeks were analyzed. Our data showed that the majority of the early life AB-induced gut effects did not persist into adulthood, yet early life AB did impact later life gut functioning. Specifically, the proximal small intestine (SI) of adult mice treated with AB in early life was characterized by hyperproliferative crypts, increased number of Paneth cells, and alterations in enteroendocrine cell-specific gene expression profiles. The distal SI of adult mice displayed a reduced expression of antibacterial defense markers. Together, our results suggest that early life AB leads to structural and physiological changes in the adult gut, which may contribute to disease development when homeostatic conditions are under challenge.
Highlights
Life is a crucial moment in the development of mammals
We have recently demonstrated that antibiotic treatment during early life can directly affect the intestinal epithelial cell (IEC) composition and functioning, independent of the effects on the microbiome [22]
We previously showed that the intestinal permeability of P20 pups treated with the same early life AB mix was reduced compared to control pups [22]
Summary
Life is a crucial moment in the development of mammals. Events that occur during the first weeks or months after birth can imprint long-lasting effects [1,2,3,4]. Among the external factors that can affect long-term health are early life antibiotics (AB). Early life AB are used to treat gastrointestinal, skin, and ear infections. Many neonates receive AB because of suspected early onset sepsis, especially after preterm birth [9]. In the case of premature neonates, AB are used to treat sepsis or to prevent infection when newborn or maternal risk factors are present. Among the different classes of AB, the most used during early life are β-lactams (amoxicillin, ampicillin), aminoglycosides (gentamycin, amikacin), glycopeptides (vancomycin, teicoplanin), and nitroimidazoles (metronidazole)
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