目的 探讨生命早期使用抗生素对新生小鼠体重和死亡率的影响,为临床治疗提供科学依据。方法 选取40只6～8周龄雌性野生型C57BL/6小鼠和20只6～8周龄雄性野生型C57BL/6小鼠,雌性小鼠随机分成对照组和抗生素处理组,每组20只。对照组和抗生素组每2只雌性小鼠配一只雄性小鼠置于一笼中饲养12周。对照组小鼠给予正常饲料和饮水,抗生素组小鼠给予正常饲料和抗生素鸡尾酒组合饮水。每周测量新生鼠体重,检测粪便细菌DNA,统计死亡率。结果 抗生素组新生小鼠在生后1周内和1～2周内的总体死亡率均明显高于对照组(P=0.034,0.027);而生后1周内和1～2周内的死亡率无明显性别差异(P＞0.05);对照组和抗生素组新生鼠在出生后1周时的体重分别是(3.870±0.079)g、(4.050±0.050)g,两组之间差异无统计学意义(t=1.926,P=0.070)。两周时体重分别是(6.230±0.142)g、(6.770±0.141)g,抗生素新生鼠体重在出生后2周明显高于对照组(t=2.699,P=0.015,);抗生素组新生鼠在1周、2周时的粪便DNA浓度明显低于对照组(P=0.007)。结论 新生鼠早期使用抗生素明显减少了肠道细菌数量,导致体重和死亡率增加。
Abstract
Objective To explore the effect of antibiotics use in early life on weight and mortality of newborn mice . Method A total of 40 female wild-type C57BL/6 mice aged 6～8 weeks and 20 male wild-type C57BL/6 mice aged 6~8 weeks were randomly divided into control group and antibiotic treatment group, with 20 mice in each group. Two female mice in the control and antibiotic groups were paired with one male mouse in a cage for 12 weeks. The mice in the control group were given normal feed and water, while the mice in the antibiotic group were given both normal feed and antibiotic cocktail. The weight of newborn mice was measured each week, fecal bacterial DNA was tested, and mortality was counted. Results The overall mortality rate of newborn mice in the antibiotic group was significantly higher than that in the control group (P=0.034, 0.027) within 1 week and 1～2 weeks after birth. There was no significantly gender difference in mortality between 1 week and 1～2 weeks after birth (P＞0.05). The weight of newborn mice in the control group and the antibiotic group at 1 week after birth was(3.870±0.079)g and(4.050±0.050)g, respectively, with no significant difference between the two groups (t=1.926, P=0.070). At 2 weeks, the weight was (6.230±0.142)g and (6.770±0.141)g, respectively. The weight of the antibiotic newborn mice was significantly higher than that of the control group at 2 weeks after birth (t=2.699, P=0.015). Moreover, the fecal DNA concentration of newborn mice in the antibiotic group was significantly lower than that of the control group (P=0.007) at 1 week and 2 weeks. Conclusions The use of antibiotics in early life in newborn mice significantly reduces the number of intestinal bacteria, increases weight and mortality, and the mechanism remains to be further studied.
关键词
抗生素 /
联合应用 /
体重 /
死亡率 /
新生鼠
Key words
antibiotics /
cocktail /
weight /
mortality /
newborn mice
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Haeseker MB, Dukers-Muijrers NH, Hoebe CJ, et al. Trends in antibiotic prescribing in adults in dutch general practice[J]. PLoS One,2012,7(12):e51860.
[2] Cunningham SA, Kramer MR, Narayan KM. Incidence of childhood obesity in the United States[J]. N Engl J Med,2014,370(17):1660-1661.
[3] Trasande L, Blustein J, Liu M, et al. Infant antibiotic exposures and early-life body mass[J]. Int J Obes (Lond),2013,37(1):16-23.
[4] Cho I, Yamanishi S, Cox L,et al.Antibiotics in early life alter the murine colonic microbiome and adiposity[J]. Nature,2012,488(7413):621-626.
[5] Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis[J]. Cell,2004,118(2):229-241.
[6] Morgun A, Dzutsev A, Dong X, et al. Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks[J]. Gut,2015,64(11):1732-1743.
[7] Greer RL, Dong X, Moraes AC, et al. Akkermansia muciniphila mediates negative effects of ifngamma on glucose metabolism[J]. Nat Commun,2016,7:13329.
[8] Rodrigues RR, Greer RL, Dong X, et al. Antibiotic-induced alterations in gut microbiota are associated with changes in glucose metabolism in healthy mice[J]. Front Microbiol,2017,8:2306.
[9] Gulden E, Vudattu NK, Deng S, et al. Microbiota control immune regulation in humanized mice[J]. JCI Insight,2017,2(21).doi: 10.1172/jci.insight.91709.
[10] Caporaso JG, Lauber CL, Walters WA, et al. Ultra-high-throughput microbial community analysis on the illumina hiseq and miseq platforms[J]. ISME J,2012,6(8):1621-1624.
[11] Shulzhenko N, Morgun A, Hsiao W, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut[J].Nat Med,2011,17(12):1585-1593.
[12] Everard A, Geurts L, Caesar R, et al. Intestinal epithelial myd88 is a sensor switching host metabolism towards obesity according to nutritional status[J]. Nat Commun,2014,5(1):5648.
[13] Cox LM, Blaser MJ. Pathways in microbe-induced obesity[J]. Cell Metab,2013,17(6):883-894.
[14] 冯玲,杨凡. 肠道菌群与肥胖及胰岛素抵抗的关系[J]. 中国儿童保健杂志,2013,21(8):826-828.
[15] Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences[J]. Cell,2014,158(4):705-721.
[16] Murphy R, Stewart AW, Braithwaite I, et al. Antibiotic treatment during infancy and increased body mass index in boys: An international cross-sectional study[J]. Int J Obes (Lond),2014,38(8):1115-1119.
[17] LiD K, Chen H, Ferber J, et al. Infection and antibiotic use in infancy and risk of childhood obesity: A longitudinal birth cohort study[J]. Lancet Diabetes Endocrinol,2017,5(1):18-25.
[18] Bailey LC, Forrest CB, Zhang P, et al. Association of antibiotics in infancy with early childhood obesity[J]. JAMA Pediatr,2014,168(11):1063-1069.
[19] Crawford PA, Crowley JR, Sambandam N, et al. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation[J]. Proc Natl Acad Sci USA,2009,106(27):11276-11281.
[20] Mikkelsen KH, Allin KH, Knop FK. Effect of antibiotics on gut microbiota, glucose metabolism and body weight regulation: a review of the literature[J]. Diabetes Obes Metab,2016,18(5):444-453.
[21] Thaiss CA,Zmora N,Levy M,et al.The microbiome and innate immunity[J]. Nature,2016,535(7610):65-74.
[22] Tamburini S, Shen N, Wu HC, et al. The microbiome in early life: Implications for health outcomes[J]. Nat Med,2016,22(7):713-722.
[23] Kayama H, Takeda K.Functions of innate immune cells and commensal bacteria in gut homeostasis[J]. J Biochem,2016,159(2):141-149.
[24] Hamm AK, Weir TL. Editorial on "cancer and the microbiota"published in science[J]. Ann Transl Med,2015,3(13):175.
[25] Karin M, Jobin C, Balkwill F.Chemotherapy, immunity and microbiota-a new triumvirate?[J]. Nat Med,2014,20(2):126-127.
基金
陕西省自然科学基础研究(20145M4144)
PDF(719 KB)
