肠道菌群及其代谢产物在新生儿坏死性小肠结肠炎中研究现状与潜在应用思考

李禄全; 刘晓晨

doi:10.12372/jcp.2022.22e0301

临床儿科杂志 >

2022 , Vol. 40 >Issue 9: 654 - 660

DOI: https://doi.org/10.12372/jcp.2022.22e0301

专家笔谈

肠道菌群及其代谢产物在新生儿坏死性小肠结肠炎中研究现状与潜在应用思考

李禄全 ,
刘晓晨

展开

重庆医科大学附属儿童医院新生儿科儿科学重庆市重点实验室国家儿童健康与疾病临床医学研究中心儿童发育重大疾病国家国际科技合作基地儿童发育疾病研究教育部重点实验室（重庆 400014）

李禄全,儿科学博士,重庆医科大学附属儿童医院新生儿科副主任,主任医师/教授,硕士研究生导师,美国佛罗里达大学访问学者。兼任重庆市妇幼卫生学会儿童健康专业委员会生命支持学组副组长,重庆市新生儿围产医学专委会副主任委员,重庆市围产医学专委会第六届委员会新生儿窒息复苏学组组长,《Frontier in Pediatrics》海外审稿编辑,《临床儿科杂志》《中国当代儿科杂志》青年编委,《BMC Pediatrics》《重庆医科大学学报》《儿科药学杂志》特邀审稿人。发表学术论文70余篇,参编专著及本科教材4部,获得重庆市政府三等奖、重庆市卫生局二等奖各一次。

收稿日期: 2022-03-07

网络出版日期: 2022-08-26

基金资助

重庆市科卫联合医学科研基金(2022MSXM039);重庆市自然科学基金(cstc2021jcyj-msxmX0063)

收起

Research status and potential application of intestinal microbiota and its metabolites in neonatal necrotizing enterocolitis

Luquan LI ,
Xiaochen LIU

Expand

Department of Neonatology, Children’s Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China

Received date: 2022-03-07

Online published: 2022-08-26

Fold

摘要

肠道菌群及其代谢产物早期预测坏死性小肠结肠炎（NEC）是近年来研究的热点。近年研究发现NEC患儿肠道菌群不仅生物多样性较低,且菌群构成比例与健康新生儿明显不同。NEC患儿氨基酸、脂代谢以及与此相关的代谢酶类也存在异常。肠道菌群及其代谢产物在预测NEC发病及病情进展等方面有一定价值,但目前只能作为科学研究探讨的依据,临床运用尚需要高质量、多中心、大样本量临床研究予以验证。

关键词： 坏死性小肠结肠炎; 肠道菌群; 代谢产物; 标志物

本文引用格式

李禄全 , 刘晓晨 . 肠道菌群及其代谢产物在新生儿坏死性小肠结肠炎中研究现状与潜在应用思考[J]. 临床儿科杂志, 2022 , 40(9) : 654 -660 . DOI: 10.12372/jcp.2022.22e0301

Abstract

The early prediction of necrotizing enterocolitis (NEC) by intestinal microbiota and its metabolites has been a hot research topic in recent years. Recent studies have found that infants with necrotizing enterocolitis (NEC) not only have low biodiversity of the intestinal microbiota, but also the composition proportion of microbiota is significantly different from that of healthy newborns. There are also abnormalities in amino acid, lipid metabolism and related metabolic enzymes in infants with NEC. Intestinal microbiota and its metabolites have certain value in predicting the onset and progression of NEC, but they can only be used as the basis for scientific research. High-quality, multi-center, and large-scale clinical studies are needed for clinical application in the future.

Key words： necrotizing enterocolitis; intestinal microbiota; metabolite; biomarker

参考文献

[1]	Duchon J, Barbian ME, Denning PW. Necrotizing enterocolitis[J]. Clin Perinatol, 2021, 48(2): 229-250.
[2]	D'apremont I, Marshall G, Musalem C, et al. Trends in perinatal practices and neonatal outcomes of very low birth weight infants during a 16-year period at NEOCOSUR centers[J]. J Pediatr, 2020, 225: 44-50.e1.
[3]	Jones IH, Hall NJ. Contemporary outcomes for infants with necrotizing enterocolitis-a systematic review[J]. J Pediatr, 2020, 220: 86-92.
[4]	Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(10): 590-600.
[5]	Thänert R, Keen EC, Dantas G, et al. Necrotizing enterocolitis and the microbiome: Current status and future directions[J]. J Infect Dis, 2021, 223(Suppl 2): S257-S263.
[6]	Pickard JM, Zeng MY, Caruso R, et al. Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease[J]. Immunol Rev, 2017, 279(1): 70-89.
[7]	Thaiss CA, Zmora N, Levy M, et al. The microbiome and innate immunity[J]. Nature, 2016, 535(7610): 65-74.
[8]	Neu J. The microbiome during pregnancy and early postnatal life[J]. Semin Fetal Neonatal Med, 2016, 21(6): 373-379.
[9]	Singh A, Mittal M. Neonatal microbiome - a brief review[J]. J Matern Fetal Neona, 2020, 33(22): 3841.
[10]	Johnson CL, Versalovic J. The human microbiome and its potential importance to pediatrics[J]. Pediatrics, 2012, 129(5): 950-960.
[11]	Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography[J]. Nature, 2012, 486(7402): 222-227.
[12]	Gasparrini AJ, Wang B, Sun X, et al. Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome[J]. Nat Microbiol, 2019, 4(12): 2285-2297.
[13]	Bäckhed F, Roswall J, Peng Y, et al. Dynamics and Stabilization of the human gut microbiome during the first year of life[J]. Cell Host Microbe, 2015, 17(5): 690-703.
[14]	Zanella A, Silveira RC, Roesch LFW, et al. Influence of own mother's milk and different proportions of formula on intestinal microbiota of very preterm newborns[J]. PLoS One, 2019, 14(5): e0217296.
[15]	Zwittink RD, Renes IB, Van Lingen RA, et al. Association between duration of intravenous antibiotic administration and early-life microbiota development in late-preterm infants[J]. Eur J Clin Microbiol Infect Dis, 2018, 37(3): 475-483.
[16]	Yao Y, Cai X, Ye Y, et al. The role of microbiota in infant health: from early life to adulthood[J]. Front Immunol, 2021, 12: 708472.
[17]	Basu S. Neonatal sepsis: the gut connection[J]. Eur J Clin Microbiol Infect Dis, 2015, 34(2): 215-222.
[18]	Ferraris L, Butel MJ, Campeotto F, et al. Clostridia in premature neonates' gut: incidence, antibiotic susceptibility, and perinatal determinants influencing colonization[J]. PLoS One, 2012, 7(1): e30594.
[19]	Kapourchali FR, Cresci GAM. Early-life gut microbiome-The importance of maternal and infant factors in its establishment[J]. Nutr Clin Pract, 2020, 35(3): 386-405.
[20]	Milani C, Duranti S, Bottacini F, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota[J]. Microbiol Mol Biol Rev, 2017, 81(4): e00036-17.
[21]	Claud EC, Keegan KP, Brulc JM, et al. Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants[J]. Microbiome, 2013, 1(1): 20.
[22]	Fu X, Li S, Jiang Y, et al. Necrotizing enterocolitis and intestinal microbiota: The timing of disease and combined effects of multiple species[J]. Front Pediatr, 2021, 9: 657349.
[23]	Liu J, Li Y, Feng Y, et al. Patterned progression of gut microbiota associated with necrotizing enterocolitis and late onset sepsis in preterm infants: a prospective study in a Chinese neonatal intensive care unit[J]. PeerJ, 2019, 7: e7310.
[24]	Mai V, Torrazza RM, Ukhanova M, et al. Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants[J]. PLoS One, 2013, 8(1): e52876.
[25]	Mai V, Young CM, Ukhanova M, et al. Fecal microbiota in premature infants prior to necrotizing enterocolitis[J]. PLoS One, 2011, 6(6): e20647.
[26]	Stewart CJ, Embleton ND, Marrs ECL, et al. Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease[J]. Microbiome, 2016, 4(1): 67.
[27]	Pammi M, Cope J, Tarr PI, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis[J]. Microbiome, 2017, 5(1): 31.
[28]	Warner BB, Tarr PI. Necrotizing enterocolitis and preterm infant gut bacteria[J]. Semin Fetal Neonatal Med, 2016, 21(6): 394-399.
[29]	Zhou Y, Shan G, Sodergren E, et al. Longitudinal analysis of the premature infant intestinal microbiome prior to necrotizing enterocolitis: a case-control study[J]. PLoS One, 2015, 10(3): e0118632.
[30]	Torrazza RM, Ukhanova M, Wang X, et al. Intestinal microbial ecology and environmental factors affecting necrotizing enterocolitis[J]. PLoS One, 2013, 8(12): e83304.
[31]	Dobbler PT, Procianoy RS, Mai V, et al. Low microbial diversity and abnormal microbial succession is associated with necrotizing enterocolitis in preterm infants[J]. Front Microbiol, 2017, 8: 2243.
[32]	Mcmurtry VE, Gupta RW, Tran L, et al. Bacterial diversity and Clostridia abundance decrease with increasing severity of necrotizing enterocolitis[J]. Microbiome, 2015, 3: 11.
[33]	Tarracchini C, Milani C, Longhi G, et al. Unraveling the microbiome of necrotizing enterocolitis: insights in novel microbial and metabolomic biomarkers[J]. Microbiol Spectr, 2021, 9(2): e0117621.
[34]	Heida FH, Van Zoonen AGJF, Hulscher JBF, et al. A necrotizing enterocolitis-associated gut microbiota is present in the meconium: results of a prospective study[J]. Clin Infect Dis, 2016, 62(7): 863-870.
[35]	Warner BB, Deych E, Zhou Y, et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study[J]. Lancet, 2016, 387(10031): 1928-1936.
[36]	Gopalakrishna KP, Macadangdang BR, Rogers MB, et al. Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants[J]. Nat Med, 2019, 25(7): 1110-1115.
[37]	Jovel J, Patterson J, Wang W, et al. Characterization of the gut microbiome using 16S or shotgun metagenomics[J]. Front Microbiol, 2016, 7: 459.
[38]	Sinclair TJ, Ye C, Chen Y, et al. Progressive metabolic dysfunction and nutritional variability precedes necrotizing enterocolitis[J]. Nutrients, 2020, 12(5): 1275.
[39]	Renwick VL, Stewart CJ. Exploring functional metabolites in preterm infants[J]. Acta paediatrica (Oslo, Norway: 1992), 2022, 111(1): 45-53.
[40]	Sekar K, Linker SM, Nguyen J, et al. Bacterial glycogen provides short-term benefits in changing environments[J]. Appl Environ Microbiol, 2020, 86(9): e00049-20.
[41]	Picaud JC, De Magistris A, Mussap M, et al. Urine NMR metabolomics profile of preterm infants with necrotizing enterocolitis over the first two months of life: a pilot longitudinal case-control study[J]. Front Mol Biosci, 2021, 8: 680159.
[42]	Reese AT, Cho EH, Klitzman B, et al. Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut[J]. Elife, 2018, 7: e35987.
[43]	Thomaidou A, Chatziioannou AC, Deda O, et al. A pilot case-control study of urine metabolomics in preterm neonates with necrotizing enterocolitis[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2019, 1117: 10-21.
[44]	Morrow AL, Lagomarcino AJ, Schibler KR, et al. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants[J]. Microbiome, 2013, 1(1): 13.
[45]	He Y, Du W, Xiao S, et al. Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells[J]. J Transl Med, 2021, 19(1): 510.
[46]	Stewart CJ, Embleton ND, Marrs EC, et al. Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease[J]. Microbiome, 2016, 4(1): 67.
[47]	Sim K, Shaw A G, Randell P, et al. Dysbiosis anticipating necrotizing enterocolitis in very premature infants[J]. Clin Infect Dis, 2015, 60(3): 389-397.
[48]	Olm MR, Bhattacharya N, Crits-Christoph A, et al. Necrotizing enterocolitis is preceded by increased gut bacterial replication, and fimbriae-encoding bacteria[J]. Sci Adv, 2019, 5(12): eaax5727.
[49]	Rusconi B, Jiang X, Sidhu R, et al. Gut sphingolipid composition as a prelude to necrotizing enterocolitis[J]. Sci Rep, 2018, 8(1): 10984.
[50]	Sylvester KG, Kastenberg ZJ, Moss RL, et al. Acylcarnitine Profiles Reflect Metabolic Vulnerability for Necrotizing Enterocolitis in Newborns Born Premature[J]. J Pediatr, 2017, 181: 80-85.e1.
[51]	Fu CY, Li LQ, Yang T, et al. Autoinducer-2 may be a new biomarker for monitoring neonatal necrotizing enterocolitis[J]. Front Cell Infect Microbiol, 2020, 10: 140.
[52]	De Meij TGJ, Van Der Schee MPC, Berkhout DJC, et al. Early detection of necrotizing enterocolitis by fecal volatile organic compounds analysis[J]. J Pediatr, 2015, 167(3): 562-567. e1.
[53]	Probert C, Greenwood R, Mayor A, et al. Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: the DOVE study[J]. Arch Dis Child Fetal Neonatal Ed, 2020, 105(5): 474-479.
[54]	Garner CE, Ewer AK, Elasouad K, et al. Analysis of faecal volatile organic compounds in preterm infants who develop necrotising enterocolitis: a pilot study[J]. J Pediatr Gastroenterol Nutr, 2009, 49(5): 559-565.

Options

文章导航

模态框（Modal）标题

摘要

本文引用格式

Abstract

参考文献