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Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

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Abstract

Background

Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency in neonates. We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates.

Methods

Using the 16S ribosomal DNA (rDNA) sequencing method, we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates: patients undergoing jejunostomy to treat NEC (NP group), neonates undergoing jejunostomy to treat other conditions (NN group), and neonates with NEC undergoing conservative treatment (NC group). We took intestinal feces and saliva samples from patients at different time points.

Results

The beta diversities of the NP, NN, and NC groups were all similar. When comparing the beta diversities between different time points in the NP group, we found similar beta diversities at time points E1 to E3 but significant differences between the E2–E3 and E4 time points: the abundances of Klebsiella and Enterococcus (Proteobacteria) were higher at the E1–E3 time points; the abundance of Escherichia-Shigella (Proteobacteria) increased at the E2 time point, and the abundance of Klebsiella decreased significantly, whereas that of Streptococcus increased significantly at the E4 time point.

Conclusions

Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine. The sources of microbiota in the small intestine of neonates, especially in premature infants, may be affected by multiple factors.

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Data availability statement

The datasets generated during and/or analyzed during the current study are not publicly available due to the rules of General Hospital of the People's Liberation Army but are available from the corresponding author on reasonable request.

References

  1. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006;368:1271–83.

    Article  PubMed  Google Scholar 

  2. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364:255–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zozaya C, García González I, Avila-Alvarez A, Oikonomopoulou N, Sánchez Tamayo T, Salguero E, et al. Incidence, treatment, and outcome trends of necrotizing enterocolitis in preterm infants: a multicenter cohort study. Front Pediatr. 2020;8:188.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Claud EC, Walker WA. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J. 2001;15:1398–403.

    Article  CAS  PubMed  Google Scholar 

  5. Brehin C, Dubois D, Dicky O, Breinig S, Oswald E, Serino M. Evolution of gut microbiome and metabolome in suspected necrotizing enterocolitis: a case-control study. J Clin Med. 2020;9:2278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hackam DJ, Sodhi CP. Bench to bedside—new insights into the pathogenesis of necrotizing enterocolitis. Nat Rev Gastroenterol Hepatol. 2022;19:468–79.

    Article  CAS  PubMed  Google Scholar 

  7. Tropini C, Earle KA, Huang KC, Sonnenburg JL. The Gut Microbiome: Connecting Spatial Organization to Function. Cell Host Microbe. 2017;21:433–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, et al. The long-term stability of the human gut microbiota. Science. 2014;341:1237439.

    Article  Google Scholar 

  9. Seedorf H, Griffin NW, Ridaura VK, Reyes A, Cheng J, Rey FE, Smith MI, et al. Bacteria from diverse habitats colonize and compete in the mouse gut. Cell. 2014;159:253–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1:6–14.

    Article  Google Scholar 

  11. Leser TD, Molbak L. Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the host. Environ Microbiol. 2009;11:2194–206.

    Article  CAS  PubMed  Google Scholar 

  12. Booijink CC, El-Aidy S, Rajilic-Atojanovic M, Heilig HG, Troost FJ, Smidt H, et al. High temporal and interindividual variation detected in the human ileal microbita. Environ Microbiol. 2010;12:3213–27.

    Article  CAS  PubMed  Google Scholar 

  13. Zoetendal EG, Raes J, van den Bogert B, Arumugam M, Booijink CC, Troost FJ, et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012;6:1414–26.

    Article  Google Scholar 

  14. Pammi M, Cope J, Tarr PI, Warner BB, Morrow AL, Mai V, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome. 2017;5:31.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci. 2010;107:11971–5.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  16. Stokholm J, Thorsen J, Chawes BL, Schjørring S, Krogfelt KA, Bønnelykke K, et al. Cesarean section changes neonatal gut colonization. J Allergy Clin Immunol. 2016;138:881–9.

    Article  PubMed  Google Scholar 

  17. Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016;8:343.

    Article  Google Scholar 

  18. Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;451:690–703.

    Article  Google Scholar 

  19. Baumann-Dudenhoeffer AM, D’Souza AW, Tarr PI, Warner BB, Dantas G. Infant diet and maternal gestational weight gain predict early metabolic maturation of gut microbiomes. Nat Med. 2018;24:1822–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yassour M, Vatanen T, Siljander H, Hämäläinen AM, Härkönen T, Ryhänen SJ, et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med. 2016;8:34381.

  21. Stewart CJ, Ajami NJ, O’Brien JL, Hutchinson DS, Smith DP, Wong MC, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562:583–8.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  22. Coggins SA, Wynn JL, Weitkamp JH. Infectious causes of necrotizing enterocolitis. Clin Perinatol. 2015;42:133–54.

    Article  PubMed  Google Scholar 

  23. Bagci S, Eis-Hubinger AM, Franz AR. Detection of astrovirus in premature infants with necrotizing enterocolitis. Pediatr Infect Dis J. 2008;27:347–50.

    Article  PubMed  Google Scholar 

  24. Stuart RL, Tan K, Mahar JE. An outbreak of necrotizing enterocolitis associated with norovirus genotype GII.3. Pediatr Infect Dis J. 2010;29:644–7.

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the children who participated in the study and the support of the General Hospital of the People's Liberation Army for this work.

Funding

This work was sponsored by the National Key R&D Program of China (No. 2022YFC2703400, to Yan Wang). This work has been funded by the Health Bureau of the Logistics Support Department of the Military Commission (Grant no.21JSZ18, to Liu-Ming Huang).

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Authors and Affiliations

  1. Clinical Biobank Center, Medical Innovation Research Division of Chinese, PLA General Hospital, Beijing, China

    Yan Wang, Xia Kang, Shan Wang, Ji-Hong Yu, Wen-Feng Ni & Xiao-Qin Qi

  2. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Kun Jiang

  3. Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, 100700, China

    Qiao Xia, Ying-Na Zhang, Jin-Bao Han, Gang Liu, Zhi-Chun Feng & Liu-Ming Huang

  4. Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China

    Lei Hou

  5. Department of Emergency Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, 100045, China

    Liu-Ming Huang

Authors
  1. Yan Wang
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  2. Kun Jiang
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  3. Qiao Xia
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  4. Xia Kang
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  5. Shan Wang
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  11. Gang Liu
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  12. Lei Hou
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Contributions

WY: conceptualization, investigation, formal analysis, writing–original draft, funding acquisition, writing–review & editing. JK, XQ: conceptualization, investigation, formal analysis, writing–original draft. KX, WS, YJH, GL: conceptualization, formal analysis. NWF, QXQ, ZYN, HJB: investigation, formal analysis. HL, FZC, HLM: funding acquisition, conceptualization, investigation, writing–review & editing. WY, JK and XQ contributed equally to this work.

Corresponding authors

Correspondence to Lei Hou, Zhi-Chun Feng or Liu-Ming Huang.

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Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Ethical approval

Ll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and approved by the Institutional Ethics Committee of PLA General Hospital.

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Wang, Y., Jiang, K., Xia, Q. et al. Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis. World J Pediatr 20, 165–172 (2024). https://doi.org/10.1007/s12519-023-00756-0

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  • DOI: https://doi.org/10.1007/s12519-023-00756-0

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