Division of Systems Biology, National Center for Toxicological Research, US FDA, Jefferson, AR 72079, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Aug 1;932:134-43. doi: 10.1016/j.jchromb.2013.05.030. Epub 2013 Jun 7.
Penicillin (PEN) V, a well-known antibiotic widely used in the treatment of Gram-positive bacterial infections, was evaluated in this study. LC/MS- and NMR-based metabolic profiling were employed to examine the effects of PEN on the host's metabolic phenotype. Male Sprague Dawley rats were randomly divided into groups that were orally administered either 0.5% methylcellulose vehicle, 100 or 2400mg PEN/kg body weight once daily for up to 14 consecutive days. Urine, plasma and tissue were collected from groups sacrificed at 6h, 24h or 14d. The body fluids were subjected to clinical chemistry and metabolomics analysis; the tissue samples were processed for histopathology. The only notable clinical chemistry observation was that gamma glutamyltransferase (GGT) significantly decreased at 24h for both dose groups, and significantly decreased at 14d for the high-dose groups. Partial least squares discriminant analysis scores plots of the metabolomics data from urine and plasma samples showed dose- and time-dependent grouping patterns. Time- and dose-dependent decreases in urinary metabolites including indole-containing metabolites (such as 3-methyldioxyindole sulfate generated from bacterial metabolism of tryptophan), organic acids containing phenyl groups (such as hippuric acid, phenyllactic acid and 3-hydroxyanthranilic acid), and metabolites conjugated with sulfate or glucuronide (such as cresol sulfate and aminophenol sulfate) indicated that the gut microflora population was suppressed. Decreases in many host-gut microbiota urinary co-metabolites (indole- and phenyl-containing metabolites, amino acids, vitamins, nucleotides and bile acids) suggested gut microbiota play important roles in the regulation of host metabolism, including dietary nutrient absorption and reprocessing the absorbed nutrients. Decreases in urinary conjugated metabolites (sulfate, glucuronide and glycine conjugates) implied that gut microbiota might have an impact on chemical detoxification mechanisms. In all, these results clearly show that metabolic profiling is a useful tool to better understand the effects of the antibiotic penicillin has on the gut microbiota and the host.
本研究评估了一种广为人知的抗生素青霉素 V（PEN）V，该抗生素常用于治疗革兰氏阳性细菌感染。采用 LC/MS 和 NMR 代谢组学方法来研究 PEN 对宿主代谢表型的影响。雄性 Sprague Dawley 大鼠随机分为三组，分别经口给予 0.5%甲基纤维素载体、100 或 2400mg PEN/kg 体重，每天 1 次，连续 14 天。在处死的 6h、24h 或 14d 时，从各组采集尿液、血浆和组织。对体液进行临床化学和代谢组学分析；对组织样本进行组织病理学处理。唯一值得注意的临床化学观察结果是，两个剂量组的γ-谷氨酰转移酶（GGT）在 24h 时显著降低，高剂量组在 14d 时显著降低。尿液和血浆样本代谢组学数据的偏最小二乘判别分析得分图显示出剂量和时间依赖性分组模式。尿液代谢物（包括细菌代谢色氨酸产生的 3-甲氧基二吲哚硫酸盐等吲哚类代谢物、含苯基团的有机酸（如马尿酸、苯乳酸和 3-羟基邻氨基苯甲酸）以及与硫酸盐或葡萄糖醛酸共轭的代谢物（如甲酚硫酸盐和对氨基酚硫酸盐））随时间和剂量的降低表明肠道微生物种群受到抑制。许多宿主-肠道微生物群尿液共代谢物（吲哚和苯类代谢物、氨基酸、维生素、核苷酸和胆汁酸）的减少表明肠道微生物群在调节宿主代谢中起着重要作用，包括膳食营养吸收和再加工吸收的营养物质。尿液共轭代谢物（硫酸盐、葡萄糖醛酸和甘氨酸共轭物）的减少表明肠道微生物群可能对化学解毒机制有影响。总之，这些结果清楚地表明，代谢组学是一种有用的工具，可以更好地了解抗生素青霉素对肠道微生物群和宿主的影响。
