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基于 NMR 的代谢组学分析,口服广谱抗生素恩诺沙星(拜有利)后小鼠尿液和粪便提取物的变化。

NMR-based metabonomics analysis of mouse urine and fecal extracts following oral treatment with the broad-spectrum antibiotic enrofloxacin (Baytril).

机构信息

Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA.

出版信息

Magn Reson Chem. 2009 Dec;47 Suppl 1:S36-46. doi: 10.1002/mrc.2511.

Abstract

The human gastrointestinal tract is home to hundreds of species of bacteria and the balance between beneficial and pathogenic bacteria plays a critical role in human health and disease. The human infant, however, is born with a sterile gut and the complex gastrointestinal host/bacterial ecosystem is only established after birth by rapid bacterial colonization. Composition of newborn gut flora depends on several factors including type of birth (Ceasarian or natural), manner of early feeding (breast milk or formula), and exposure to local, physical environment. Imbalance in normal, healthy gut flora contributes to several adult human diseases including inflammatory bowel (ulcerative colitis and Crohn's disease) and Clostridium difficile associated disease, and early childhood diseases such as necrotizing enterocolitis. As a first step towards characterization of the role of gut bacteria in human health and disease, we conducted an 850 MHz (1)H nuclear magnetic resonance spectroscopy study to monitor changes in metabolic profiles of urine and fecal extracts of 15 mice following gut sterilization by the broad-spectrum antibiotic enrofloxacin (also known as Baytril). Ten metabolites changed in urine following enrofloxacin treatment including decreased acetate due to loss of microbial catabolism of sugars and polysaccharides, decreased trimethylamine-N-oxide due to loss of microbial catabolism of choline, and increased creatine and creatinine due to loss of microbial enzyme degradation. Eight metabolites changed in fecal extracts of mice treated with enrofloxacin including depletion of amino acids produced by microbial proteases, reduction in metabolites generated by lactate-utilizing bacteria, and increased urea caused by loss of microbial ureases.

摘要

人体胃肠道是数百种细菌的家园,有益菌和致病菌之间的平衡对人类健康和疾病起着至关重要的作用。然而,人类婴儿出生时肠道是无菌的,只有在出生后,通过快速的细菌定植,复杂的胃肠道宿主/细菌生态系统才得以建立。新生儿肠道菌群的组成取决于多种因素,包括分娩方式(剖腹产或自然分娩)、早期喂养方式(母乳或配方奶)以及对当地物理环境的暴露。正常健康的肠道菌群失衡会导致几种人类成年疾病,包括炎症性肠病(溃疡性结肠炎和克罗恩病)和与艰难梭菌相关的疾病,以及幼儿疾病,如坏死性小肠结肠炎。为了研究肠道细菌在人类健康和疾病中的作用,我们首先进行了一项 850MHz(1)H 核磁共振波谱研究,以监测 15 只小鼠在广谱抗生素恩诺沙星(也称为拜有利)肠道灭菌后尿液和粪便提取物代谢谱的变化。恩诺沙星治疗后尿液中有 10 种代谢物发生变化,包括由于微生物对糖和多糖的代谢减少而导致的乙酸盐减少、由于微生物对胆碱的代谢减少而导致的三甲胺-N-氧化物减少、由于微生物酶降解减少而导致的肌酸和肌酐增加。在接受恩诺沙星治疗的小鼠的粪便提取物中有 8 种代谢物发生变化,包括微生物蛋白酶产生的氨基酸耗竭、利用乳酸的细菌产生的代谢物减少以及微生物脲酶减少导致的尿素增加。

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