Prolonged antibiotic use induces intestinal injury in mice that is repaired after removing antibiotic pressure: implications for empiric antibiotic therapy.
Prolonged antibiotic use induces intestinal injury in mice that is repaired after removing antibiotic pressure: implications for empiric antibiotic therapy.
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长期使用抗生素会导致小鼠肠道损伤，而肠道损伤在消除抗生素压力后会得到修复：对经验性抗生素治疗的影响。
DOI：
10.1007/s11306-013-0546-5
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kennedy,MichaelA
中科院分区：
文献类型：
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作者：
Romick-Rosendale,LindseyE;Legomarcino,Anne;Patel,NeilB;Morrow,ArdytheL;Kennedy,MichaelA
尿液和粪便提取物的代谢谱、肠回肠的组织学研究和粪便宏基因组学分析用于研究小鼠中长期使用抗生素的影响。这项研究提供了对人类延长经验性抗生素治疗效果的深入了解。小鼠连续四天给予广谱抗生素，然后口服丁酸梭菌，一种常见于坏死性小肠结肠炎患者粪便和血液培养中的机会性革兰氏阳性致病菌。宏基因组学数据表明，抗生素4天后细菌多样性丧失，在消除抗生素压力后恢复。组织学分析表明抗生素治疗后回肠绒毛受损，在解除抗生素压力后进行修复。代谢分析证实了经直肠给药小鼠的肠损伤，表现为尿反式-4-羟基-1-脯氨酸增加，这是回肠绒毛结缔组织中胶原蛋白的分解产物，可作为高危人群中直肠给药诱导损伤的生物标志物。
Metabolic profiling of urine and fecal extracts, histological investigation of intestinal ilea, and fecal metagenomics analyses were used to investigate effects of prolonged antibiotic use in mice. The study provides insight into the effects of extended empiric antibiotic therapy in humans. Mice were administered a broad-spectrum antibiotic for four consecutive days followed by oral gavage withClostridium butyricum,an opportunistic gram-positive pathogenic bacteria commonly isolated in fecal and blood cultures of necrotizing enterocolitis patients. Metagenomics data indicated loss of bacterial diversity after 4 days on antibiotics that was restored after removing antibiotic pressure. Histological analyses indicated damage to ileal villi after antibiotic treatment that underwent repair after lifting antibiotic pressure. Metabolic profiling confirmed intestinal injury in antibiotic-treated mice indicated by increased urinary trans-4-hydroxy-l-proline, a breakdown product of collagen present in connective tissue of ileal villi that may serve as a biomarker for antibiotic-induced injury in at risk populations.