早发型败血症所致新生儿高胆红素血症的肠道菌群结构变化分析

沈男; 乔继冰; 蒋亚洲; 吴让; 于乔; 朱苏月

doi:10.16766/j.cnki.issn.1674-4152.003964

早发型败血症所致新生儿高胆红素血症的肠道菌群结构变化分析

doi: 10.16766/j.cnki.issn.1674-4152.003964

徐州医科大学附属宿迁医院儿科，江苏宿迁 223800

基金项目:

江苏省妇幼健康科研项目 F202153

详细信息

通讯作者:
朱苏月，E-mail：zsyzsy7878@163.com

中图分类号: R722 R446.13
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出版历程
- 收稿日期: 2024-04-10
- 网络出版日期: 2025-06-30

Analysis of changes in gut microbiota structure in neonatal hyperbilirubinemia caused by early-onset sepsis

Department of Pediatrics, Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, Jiangsu 223800, China

摘要

摘要: 目的利用高通量测序技术对早发型败血症(EOS)所致新生儿高胆红素血症(NH)的肠道菌群结构进行测定并分析其变化特点。方法选取2022年12月—2023年7月在徐州医科大学附属宿迁医院确诊为EOS所致NH患儿25例，以及同期在该院出生的健康新生儿26名，分别作为NH组和对照组。收集所有新生儿粪便样本并提取DNA，质检合格后行16S rDNA扩增子测序。选用α多样性分析中Shannon指数和ace指数分别比较2组间的菌群多样性和丰度差异；β多样性分析中加权unifrac距离比较结构相似性。通过LDA和LEfSe分析对差异菌进行多水平对比，并对2组中占比前十的菌种进行丰度比较，筛选出生物标记物。结果 2组共获取OTU 281个，其中NH组157个，对照组124个，2组相同的有66个。NH组Shannon指数和ace指数均升高，但仅Shannon指数差异有统计学意义(P＜0.05)。NH组关键菌种(生物标记物)中唾液链球菌(P＜0.05)丰度降低，大肠杆菌(P＜0.05)、肺炎克雷伯杆菌(P＜0.05)和口腔链球菌(P＜0.05)丰度升高。结论 EOS所致NH的肠道菌群多样性增加；门、属水平变化最大的菌类为厚壁菌门和埃希氏菌属；关键菌种改变以有益菌丰度降低和机会致病菌丰度升高为主要特点。
- 早发型败血症 /
- 新生儿高胆红素血症 /
- 肠道菌群
Abstract: Objective The utilization of high-throughput sequencing technology facilitates the elucidation of the gut microbiota structure and the alterations in neonatal hyperbilirubinemia (NH) occasioned by early onset-sepsis (EOS). Methods A total of 25 children diagnosed with NH caused by EOS in Suqian Hospital Affiliated to Xuzhou Medical University from December 2022 to July 2023, and 26 healthy newborns born during the same period were included in the study. The NH group and the control group were defined, respectively. All newborn stool samples were collected and DNA was extracted. 16S rDNA amplicon sequencing was performed after passing the quality inspection. The Shannon index and ace index, which are used to assess diversity, were employed to compare the richness and diversity between the two groups. The structural similarity of microbiota was compared using the weighted unifrac distance in the β diversity analysis. To identify significant differences in bacteria at multiple levels, the linear discriminant analysis (LDA) and LDA Effect Size (LEfSe) analyses were used. Finally, the richness of the top ten strains in the two groups was compared and the biomarkers were screened. Results A total of 281 operational taxonomic units (OTUs) were obtained in the two groups, including 157 in the NH group, 124 in the control group, and the same 66 OTUs. The Shannon and Ace indices exhibited an increase in the NH group, with the Shannon index demonstrating statistical significance (P < 0.05). The key bacterial species (biomarkers) in the NH group are characterized by a decrease in the richness of Streptococcus salivarius (P < 0.05), and an increase in the richness of Escherichia (P < 0.05), Klebsiella pneumoniae (P < 0.05), and Streptococcus oralis (P < 0.05). Conclusion The diversity of the gut microbiota has been observed to increase in newborns with NH caused by EOS. At the phylum and genus levels, the most significant changes in NH group abundance were observed to be Firmicutes and Escherichia. The shift in key species was characterized by a decrease in beneficial bacteria and an increase in opportunistic pathogenic bacteria.
- Early-onset sepsis /
- Neonatal hyperbilirubinemia /
- Intestinal flora

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图 1 2组新生儿肠道菌群在门水平和属水平的主要菌类比较

注：A为门水平菌类相对丰度比较，B为属水平菌类相对丰度比较。

Figure 1. Comparison of dominant gut microbiota between two groups of newborns at the phylum and genus levels

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图 2 NH组和对照组新生儿肠道菌群中LDA分值大于预设值的显著差异物种

Figure 2. Significantly differential gut microbial species between NH and control newborn groups with LDA scores exceeding the threshold

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图 3 NH组和对照组新生儿肠道菌群中的关键物种差异性比较

Figure 3. Comparison of key gut microbial species between NH and control newborn groups

下载: 全尺寸图片幻灯片

参考文献(20)

[1]	QATTEA I, FARGHALY M A A, ELGENDY M, et al. Neonatal hyperbilirubinemia and bilirubin neurotoxicity in hospitalized neonates: analysis of the US database[J]. Pediatr Res, 2022, 91(7): 1662-1668. doi: 10.1038/s41390-021-01692-3
[2]	BRIGGS-STEINBERG C, ROTH P. Early-onset sepsis in newborns[J]. Pediatr Rev, 2023, 44(1): 14-22. doi: 10.1542/pir.2020-001164
[3]	王洁洁, 王国凯. 茵栀黄口服液联合双歧杆菌四联活菌治疗新生儿黄疸的效果分析[J]. 中华全科医学, 2022, 20(7): 1158-1161. doi: 10.16766/j.cnki.issn.1674-4152.002547 WANG J J, WANG G K. Analysis of the curative effect of of Yinzhihuang oral liquid combined with bifidobacterium tetragenous viable bacteria in the treatment of neonatal jaundice[J]. Chinese Journal of General Practice, 2022, 20(7): 1158-1161. doi: 10.16766/j.cnki.issn.1674-4152.002547
[4]	TSAI M L, LIN W Y, CHEN Y T, et al. Adjuvant probiotic Bifidobacterium animalis subsp. lactis CP-9 improve phototherapeutic treatment outcomes in neonatal jaundice among full-term newborns: a randomized double-blind clinical study[J]. Medicine(Baltimore), 2022, 101(45): e31030. DOI: 10.1097/MD.0000000000031030.
[5]	CHEN K W, YUAN T M. The role of microbiota in neonatal hyperbilirubinemia[J]. Am J Transl Res, 2020, 12(11): 7459-7474.
[6]	KEMPER A R, NEWMAN T B, SLAUGHTER J L, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation[J]. Pediatrics, 2022, 150(3): e2022058859. DOI: 10.1542/peds.2022-058859.
[7]	中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识(2019年版)[J]. 中华儿科杂志, 2019, 57(4): 252-257. Subspecialty Group of Neonatology, the Society of Pediatric, Chinese Medical Association, Professional Committee of Infectious Diseases, Neonatology Society, Chinese Medical Doctor Association. Expert consensus on the diagnosis and management of neonatal sepsis (version 2019)[J]. Chinese Journal of Pediatrics, 2019, 57(4): 252-257.
[8]	DING J, MA X, HAN L P, et al. Gut microbial alterations in neonatal jaundice pre-and post-treatment[J]. Biosci Rep, 2021, 41(4): BSR20210362. DOI: 10.1042/BSR20210362.
[9]	霍晨达. 基于16s rRNA高通量测序技术对恶性梗阻性黄疸围手术期肠道菌群多样性改变的研究[D]. 太原: 山西医科大学, 2023. HUO C D. Research of the gut microbiota diversity in patients with malignant obstructive jaundice during the perioperative period based on 16S rRNA sequencing[D]. Taiyuan: Shanxi Medical University, 2023.
[10]	贾尔肯阿依·阿不都拉依, 寇新红, 陈凤娟, 等. 迟发型母乳性黄疸患儿肠道菌群特征研究[J]. 中国妇幼卫生杂志, 2022, 13(1): 57-61. JIAERKENAYI A, KOU X H, CHEN F J, et al. Characteristics of intestinal flora in children with late onset breast milk jaundice[J]. Chinese Journal of Women and Children Health, 2022, 13(1): 57-61.
[11]	赵力锐, 徐艳, 叶黎离, 等. 未足月胎膜早破早产儿早发败血症肠道菌群的特征及临床意义[J]. 徐州医科大学学报, 2021, 41(4): 289-294. ZHAO L R, XU Y, YE L L, et al. Characteristics and clinical significance of intestinal microbiota in early-onset sepsis of pretern infants with premature rupture of membranes[J]. Journal of Xuzhou Medical University, 2021, 41(4): 289-294.
[12]	BROWNE H P, SHAO Y, LAWLEY T D. Mother-infant transmission of human microbiota[J]. Curr Opin Microbiol, 2022, 69: 102173. DOI: 10.1016/j.mib.2022.102173.
[13]	陶丽梅, 姜春明. 肠道菌群和黄疸的研究进展[J]. 中国微生态学杂志, 2021, 33(1): 112-115. TAO L M, JIANG C M. Progress in research on intestinal flora and jaundice[J]. Chinese Journal of Microecology, 2021, 33(1): 112-115.
[14]	MUTLU M, ASLAN Y, KADER S, et al. Preventive effects of probiotic supplementation on neonatal hyperbilirubinemia caused by isoimmunization[J]. Am J Perinatol, 2020, 37(11): 1173-1176.
[15]	CHOUDHARY P, KRAATZ H B, LEVESQUE C M, et al. Microencapsulation of Probiotic Streptococcus salivarius LAB813[J]. ACS Omega, 2023, 8(13): 12011-12018.
[16]	LAO J, GUÉDON G, LACROIX T, et al. Abundance, diversity and role of ICEs and IMEs in the adaptation of Streptococcus salivarius to the environment[J]. Genes(Basel), 2020, 11(9): 999. DOI: 10.3390/genes11090999.
[17]	KOMSANI M R, ALMAGHLOUTH N K, CHARLA S, et al. Escherichia coli meningitis in a 72-year-old woman[J]. R I Med J, 2024, 107(1): 12-14.
[18]	CUI M M, SUN W, XUE Y, et al. Hepatitis E virus and Klebsiella pneumoniae co-infection detected by metagenomics next-generation sequencing in a patient with central nervous system and bloodstream Infection: a case report[J]. BMC Infect Dis, 2024, 24(1): 33. DOI: 10.1186/s12879-023-08850-4.
[19]	唐炜, 卢红艳, 孙勤, 等. 高胆红素血症新生儿肠道菌群特点及与β-葡萄糖醛酸苷酶活性的相关性[J]. 中国当代儿科杂志, 2021, 23(7): 677-683. TANG W, LU H Y, SUN Q, et al. Characteristics of gut microbiota and its association with the activity of β-glucuronidase in neonates with hyperbilirubinemia[J]. Chinese Journal of Contemporary Pediatrics, 2021, 23(7): 677-683.
[20]	ELMASSRY M M, KIM S, BUSBY B. Predicting drug-metagenome interactions: variation in the microbial β-glucuronidase level in the human gut metagenomes[J]. PLoS One, 2021, 16(1): e0244876. DOI: 10.1371/journal.pone.0244876.