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抗生素对极早产儿肠道菌群的早期影响

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目的 探讨出生后抗生素使用时间和极早产儿肠道菌群失调的关系.方法 前瞻性选择纳入 29 例于2023 年 2 月—2023 年 9 月在南京医科大学第一附属医院住院的胎龄小于 32 周的早产儿,按照抗生素使用时间分为 7 d内组(使用抗生素 6~7 d,n=12)和>7 d组(使用抗生素 8~28 d,n=17),收集生后 7、14、21、28 d的粪便标本,采用 16S rDNA高通量测序技术检测菌群,采用生信分析、Wilcoxon秩和检验、t检验或者Fisher精确检验等对 2 组临床资料、肠道菌群以及短链脂肪酸进行分析.结果 2 组极早产儿的临床特征基本一致.2 组在 28 d内抗生素使用时间分别为 7.0(6.0,7.0)d与 13.0(9.8,19.3)d,Z=-4.61,P<0.001.总共分析了 112 份粪便标本中的 16S rDNA和 20 份标本中的短链脂肪酸.在 7 d时,2 组菌群在门、纲、目、科、属、种水平上差异均无统计学意义,2 组间Chao指数、丰度的范围评估(ACE)指数和Shannon指数差异亦无统计学意义;在 14 d时,2 组菌群出现差异,>7 d组的疣微菌门相对丰度(P=0.030)、狭义梭菌属相对丰度(P=0.039)和醋酸浓度(P=0.015)均降低;在 21 d时,菌群差异持续存在,>7 d组的疣微菌门相对丰度降低(P=0.020),而放线菌门相对丰度(P=0.048)、Shannon指数(P=0.018)升高;在 28 d时,2 组的菌群差异消失,α多样性差异无统计学意义.7 d内组的自身对比,从生后 7 d到 14 d,拟杆菌门(P=0.026)、嗜热链球菌(P=0.023)和伯克霍尔德菌(P=0.026)相对丰度明显下降,α多样性差异无统计学意义;从 14 d到 28 d,各水平上差异均无统计学意义.>7 d组的自身对比,从 7 d到 14 d以及从 14 d到 28 d,各水平上对比差异均无统计学意义.结论 出生后使用抗生素 7 d内和>7 d的极早产儿的肠道菌群在 7 d时相似,由于抗生素使用时间不同,肠道菌群在生后 14 d、21 d出现统计学差异,但在生后 28 d时,2 组肠道菌群"恢复"至相似水平.
Early effect of antibiotics on the gut microbiota of extremely preterm infants
Objective To explore the relationship between the duration of antibiotic use after birth and gut microbiota dysbiosis in extremely preterm infants.Methods A total of 29 preterm infants with gestational ages under 32 weeks who were hospitalized at the First Affiliated Hospital of Nanjing Medical University from February 2023 to September 2023 were prospectively included.According to the duration of antibiotic use,the infants were divided into two groups:a≤7-day group(antibiotics used for 6-7 days,n=12)and a>7-day group(antibiotics used for 8-28 days,n=17).Fecal samples were collected at 7,14,21,and 28 days after birth.Gut microbiota was analyzed by 16S rDNA high-throughput sequencing.Their clinical data,gut microbiota,and short-chain fatty acids(SCFAs)were analyzed by bioinformatics,Wilcoxon rank-sum tests,t-tests,or Fisher's exact tests.Results Both groups shared the same clinical features.The duration of antibiotic use within 28 days was 7.0(6.0,7.0)days for the≤7-day group and 13.0(9.8,19.3)days for the>7-day group(Z=-4.61,P<0.001).A total of 112 fecal samples were analyzed for 16S rDNA and 20 samples for SCFAs.On day 7,no statistical differences were found between the two groups at the phylum,class,order,family,genus,or species levels,nor in the Chao,ACE,or Shannon diversity indices.On day 14,significant differences emerged:the relative abundance of Verrucomicrobiota(P=0.030)and Clostridium sensu stricto(P=0.039),as well as acetate concentration(P=0.015),decreased in the>7-day group.On day 21,differences persisted,and the relative abundance of Verrucomicrobiota remained decreased(P=0.020),while the relative abundance of Actinobacteria(P=0.048)and Shannon diversity index(P=0.018)increased in the>7-day group.On day 28,these differences disappeared,and diversity showed no statistical significance between the groups.Within-group comparisons in the≤7-day group revealed a significant decline in the relative abundance of Bacteroidetes(P=0.026),Streptococcus thermophilus(P=0.023),and Burkholderia(P=0.026)from 7 to 14 days after birth,without statistical changes in diversity.From 14 to 28 days after birth,no statistical differences were observed at any taxonomic level.For the>7-day group,no statistical within-group differences were found from 7 to 14 days or from 14 to 28 days.Conclusions The gut microbiota of the two groups is similar on day 7.Due to the difference in antibiotic durations,statistical differences in gut microbiota were observed on 14 and 21 days after birth.But by 28 days after birth,the gut microbiota of both groups had"recovered"to similar levels.

extremely preterm infantsgut microbiotadysbiosisantibioticsshort-chain fatty acidshigh-throughput sequencing

宁涛、朱绿柳、彭淞、张宇涵、陈天雨、于乔、陈筱青、李冰洁

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徐州医科大学附属宿迁医院儿科,江苏 宿迁 223800

南京医科大学第一附属医院儿科,江苏 南京 210029

极早产儿 肠道菌群 菌群失调 抗生素 短链脂肪酸 高通量测序

2024

徐州医科大学学报
徐州医学院

徐州医科大学学报

CSTPCD
影响因子:0.395
ISSN:2096-3882
年,卷(期):2024.44(11)