Martins Garcia Tnia, van Roest Manon, Vermeulen Jacqueline L M, Meisner Sander, Koster Jan, Wildenberg Manon E, van Elburg Ruurd M, Muncan Vanesa, Renes Ingrid B
Department of Gastroenterology and Hepatology, Tytgat Institute for Intestinal and Liver Research, Amsterdam UMC, AGEM, University of Amsterdam, 1105 BK Amsterdam, The Netherlands.
Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Antibiotics (Basel). 2022 Feb 18;11(2):267. doi: 10.3390/antibiotics11020267.
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.
新生儿长期使用抗生素（AB）与成年后疾病发病率增加之间的关联尚未完全明确。生命早期的AB治疗会改变肠道上皮细胞的组成、功能和成熟过程，这可能是成年后健康受到影响的基础。在此，我们研究了AB诱导的新生儿肠道变化是否会持续至成年期，以及生命早期使用AB是否会对肠道功能产生额外的长期影响。小鼠从出生后第10天至20天口服AB。分析了8周龄时的肠道形态、通透性以及基因和蛋白质表达。我们的数据表明，生命早期AB诱导的大多数肠道效应不会持续至成年期，但生命早期使用AB确实会影响成年后的肠道功能。具体而言，生命早期接受AB治疗的成年小鼠的近端小肠（SI）具有隐窝过度增殖、潘氏细胞数量增加以及肠内分泌细胞特异性基因表达谱改变的特征。成年小鼠的远端SI显示抗菌防御标志物的表达降低。总之，我们的结果表明，生命早期使用AB会导致成年肠道的结构和生理变化，当体内稳态条件受到挑战时，这可能会促进疾病的发展。
