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The association between enteric viruses and necrotizing enterocolitis

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Abstract

Studies on necrotizing enterocolitis (NEC) have not largely focused on enteric viruses. In order to demonstrate the association between enteric viruses and NEC, stool specimens of 51 neonates with NEC and 39 “normal” neonates were collected to detect rotavirus (RV), astrovirus (ASV), sapovirus, enterovirus (EV), adenovirus (ADV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human bocavirus (HBoV). Rotavirus A (RVA), ASV, EBV, and ADV were detected in both the NEC and control groups; however, EV and HBoV were detected only in the NEC group and CMV was not detected in either group. ASV was the most common enteric virus, but no significant differences were found between NEC and control groups, as was similarly the case for EBV and EV. The prevalence of ADV and HBoV was higher in the NEC group than in the control group (P = 0.011, P = 0.005, respectively) but RVA showed the opposite trend (P = 0.014). Virus positivity or negativity had no influence on the clinical manifestation of NEC.

Conclusion: The roles of different viruses in NEC are not congruent. Some, such as ASV, may be regarded as commensal in neonates, while in NEC patients, the presence of ADV and EBV may be related to severity of disease.

What is known:

• The etiology of NEC remains unknown. Studies on necrotizing enterocolitis (NEC) have not largely focused on enteric viruses and the conclusions were inconsistent.

What is new:

• Enteric viruses are common in the gut of neonates, but not all of them are pathogenic.

• The existence of ADV and EBV may be related to the severity of NEC.

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Abbreviations

ADV:

Adenovirus

ASV:

Astrovirus

CMV:

Cytomegalovirus

DOL:

Day of life

EBV:

Epstein-Barr virus

EV:

Enterovirus

HBoV:

Human bocavirus

IBD:

Inflammatory bowel disease

MC:

Microscopic colitis

NEC:

Necrotizing enterocolitis

NICU:

Neonatal intensive care units

SIP:

Spontaneous intestinal perforation

RVA:

Rotavirus A

References

  1. Berrington JE, Stewart CJ, Embleton ND (2014) The neonatal bowel microbiome in health and infection. Curr Opin Infect Dis 27(3):236–243. https://doi.org/10.1097/QCO.0000000000000061

    Article  PubMed  Google Scholar 

  2. Berrington JE, Stewart CJ, Embleton ND, Cumming SP (2013) Gut microbiota in preterm infants: assessment and relevance to health and disease. Arch Dis Child Fetal Neonatal 98(4):F286–F290. https://doi.org/10.1136/archdischild-2012-302134

    Article  Google Scholar 

  3. Johnson FE, Crnic DM, Simmons MA, Lilly JR (1977) Association of fatal coxsackie B2 viral infection and necrotizing enterocolitis. Arch Dis Child 52(10):802–804. https://doi.org/10.1136/adc.52.10.802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tran L, Ferris M, Norori J, Stark M, Craver R, Dowd S, Penn D (2013) Necrotizing enterocolitis and cytomegalovirus infection in a premature infant. Pediatrics. 131(1):e318–e322. https://doi.org/10.1542/peds.2011-1971

    Article  PubMed  Google Scholar 

  5. Bagci S, Eis-Hübinger AM, Franz AR, Bierbaum G, Heep A, Schildgen O, Bartmann P, Kupfer B, Mueller A (2008) Detection of astrovirus in premature infants with necrotizing enterocolitis. Pediatr Infect Dis J 27(4):347–350. https://doi.org/10.1097/INF.0b013e318162a17a

    Article  PubMed  Google Scholar 

  6. Rotbart HA, Nelson WL, Glode MP, Triffon TC, Kogut SJ, Yolken RH, Hernandez JA, Levin MJ (1988) Neonatal rotavirus-associated necrotizing enterocolitis: case control study and prospective surveillance during an outbreak. J Pediatr 112(1):87–93. https://doi.org/10.1016/s0022-3476(88)80128-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yolken RH, Franklin CC (1985) Gastrointestinal adenovirus: an important cause of morbidity in patients with necrotizing enterocolitis and gastrointestinal surgery. Pediatr Infect Dis 4(1):42–47

    Article  CAS  Google Scholar 

  8. Chany C, Moscovici O, Lebon P, Rousset S (1982) Association of coronavirus infection with neonatal necrotizing enterocolitis. Pediatrics. 69(2):209–214

    CAS  PubMed  Google Scholar 

  9. Lodha A, de Silva N, Petric M, Moore AM (2005) Human torovirus: a new virus associated with neonatal necrotizing enterocolitis. Acta Paediatr 94(8):1085–1088. https://doi.org/10.1111/j.1651-2227.2005.tb02049.x

    Article  PubMed  Google Scholar 

  10. Peter CS, Feuerhahn M, Bohnhorst B, Schlaud M, Ziesing S, von der Hardt H, Poets CF (1999) Necrotising enterocolitis: is there a relationship to specific pathogens? Eur J Pediatr 158(1):67–70. https://doi.org/10.1007/s004310051012

    Article  CAS  PubMed  Google Scholar 

  11. Skeath T, Stewart C, Waugh S, Embleton N, Cummings S, Berrington J (2016) Cytomegalovirus and other common enteric viruses are not commonly associated with NEC. Acta Paediatr 105(1):50–52. https://doi.org/10.1111/apa.13110

    Article  PubMed  Google Scholar 

  12. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T (1978) Neonatal Necrotizing Enterocolitis. Ann Surg 187(1):1–7. https://doi.org/10.1097/00000658-197801000-00001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Singh Y, Tissot C, Fraga MV, Yousef N, Cortes RG, Lopez J, Sanchez-de-Toledo J, Brierley J, Colunga JM, Raffaj D, Da Cruz E, Durand P, Kenderessy P, Lang HJ, Nishisaki A, Kneyber MC, Tissieres P, Conlon TW, De Luca D (2020) International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). Crit Care 24(1):65. https://doi.org/10.1186/s13054-020-2787-9

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fricke WF (2014) The more the merrier? Reduced fecal microbiota diversity in preterm infants treated with antibiotics. J Pediatr 165(1):8–10. https://doi.org/10.1016/j.jpeds.2014.03.022

    Article  PubMed  Google Scholar 

  15. Minot S, Sinha R, Chen J, Li H, Keilbaugh SA, Wu GD, Lewis JD, Bushman FD (2011) The human gut virome: Inter-individual variation and dynamic response to diet. Genome Res 21(10):1616–1625. https://doi.org/10.1101/gr.122705.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon JI (2010) Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature. 466(7304):334–338. https://doi.org/10.1038/nature09199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Willner D, Furlan M, Schmieder R, Grasis JA, Pride DT, Relman DA, Angly FE, McDole T, Mariella RP Jr, Rohwer F, Haynes M (2011) Metagenomic detection of phage-encoded platelet binding factors in the human oral cavity. Proc Natl Acad Sci U S A 15:108

    Google Scholar 

  18. Gabbay YB, Luz CR, Costa IV, CavalcantePepino EL, Sousa MS, Oliveira KK, Wanzeller AL, Mascarenhas JD, Leite JP, Linhares AC (2005) Prevalence and genetic diversity of astroviruses in children with and without diarrhea in Sao Luis, Maranhao, Brazil. Mem Inst Oswaldo Cruz 100(7):709–714. https://doi.org/10.1590/s0074-02762005000700004

    Article  PubMed  Google Scholar 

  19. Mendez-Toss M, Griffin DD, Calva J, Contreras JF, Puerto FI, Mota F, Guiscafre H, Cedillo R, Munoz O, Herrera I, Lopez S, Arias CF (2004) Prevalence and genetic diversity of human astroviruses in Mexican children with symptomatic and asymptomatic infections. J Clin Microbiol 42(1):151–157. https://doi.org/10.1128/jcm.42.1.151-157.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bernstein DI (2009) Rotavirus overview. Pediatr Infect Dis J 28(3 Suppl):S50–S53. https://doi.org/10.1097/INF.0b013e3181967bee

    Article  PubMed  Google Scholar 

  21. Santosham M, Pathak A, Kottapalli S et al (1982) Neonatal rotavirus infection. Lancet. 1(8280):1070–1071

    Article  CAS  Google Scholar 

  22. Chrystie IL, Totterdell BM, Banatvalla JE (1978) Asymptomatic endemic rotavirus infections in the newborn. Lancet. 1(8075):1176–1178

    Article  CAS  Google Scholar 

  23. Sharma R, Garrison RD, Tepas JJ, Mollitt DL, Pieper P, Hudak ML, Bradshaw JA, Stevens G, Premachandra BR (2004) Rotavirus-associated necrotizing enterocolitis: an insight into a potentially preventable disease? J Pediatr Surg 39(3):453–457. https://doi.org/10.1016/j.jpedsurg.2003.11.016

    Article  PubMed  Google Scholar 

  24. Haffejee IE (1991) Neonatal Rotavirus Infections. Rev Infect Dis 13(5):957–962. https://doi.org/10.1093/clinids/13.5.957

    Article  CAS  PubMed  Google Scholar 

  25. Aktaş O, Aydin H, Timurkan MO (2019) A molecular study on the prevalence and coinfections of rotavirus, norovirus, astrovirus and adenovirus in children with gastroenteritis. Minerva Pediatr 71(5):431–437. https://doi.org/10.23736/S0026-4946.16.04304-X

    Article  PubMed  Google Scholar 

  26. Vicente D, Cilla G, Montes M, Pérez-Yarza EG, Pérez-Trallero E (2007) Human bocavirus, a respiratory and enteric virus. Emerg Infect Dis 13(4):636–637. https://doi.org/10.3201/eid1304.061501

    Article  PubMed  PubMed Central  Google Scholar 

  27. Shirani F, Teimoori A, McAinch AJ, Rashno M, Latifi SM, Karandish M (2020) Human adenovirus 36 improves insulin sensitivity and lipid profiles and increases inflammatory markers in Wistar rats. J Investig Med 68:980–984. https://doi.org/10.1136/jim-2019-001165

    Article  PubMed  Google Scholar 

  28. Campe H, Hartberger C, Sing A (2008) Role of human bocavirus infections in outbreaks of gastroenteritis. J Clin Virol 43:340–342. https://doi.org/10.1016/j.jcv.2008.07.014

    Article  PubMed  Google Scholar 

  29. Ford AC, Peyrin-Biroulet L (2013) Opportunistic infections with anti-tumor necrosis factor-alpha therapy in inflammatory bowel disease: meta-analysis of randomized controlled trials. Am J Gastroenterol 108(8):1268–1276. https://doi.org/10.1038/ajg.2013.138

    Article  CAS  PubMed  Google Scholar 

  30. Toussirot E, Roudier J (2008) Epstein–Barr virus in autoimmune diseases. Best Pract Res Clin Rheumatol 22(5):883–896. https://doi.org/10.1016/j.berh.2008.09.007

    Article  CAS  PubMed  Google Scholar 

  31. Rizzo AG, Orlando A, Gallo E, Bisanti A, Sferrazza S, Montalbano LM, Macaluso FS, Cottone M (2017) Is Epstein-Barr virus infection associated with the pathogenesis of microscopic colitis? J Clin Virol 97:1–3. https://doi.org/10.1016/j.jcv.2017.10.009

    Article  CAS  PubMed  Google Scholar 

  32. Lopes S, Andrade P, Conde S, Liberal R, Dias CC, Fernandes S, Pinheiro J, Simões JS, Carneiro F, Magro F, Macedo G (2017) Looking into enteric virome in patients with IBD: defining guilty or innocence? Inflamm Bowel Dis 23(8):1278–1284. https://doi.org/10.1097/MIB.0000000000001167

    Article  PubMed  Google Scholar 

  33. Ostlie DJ, Spilde TL, St Peter SD, Sexton N, Miller KA, Sharp RJ, Gittes GK, Snyder CL (2003) Necrotizing enterocolitis in full-term infants. J Pediatr Surg 38(7):1039–1042

    Article  Google Scholar 

  34. Qiu-Yu L, Yao A, Li L, Xue-Qiu W, Shi C, Zheng-Li W, Lu-Quan L (2017) Differences in the clinical characteristics of early- and late-onset necrotizing enterocolitis in full-term infants: a retrospective case-control study. Sci Rep 7:43042. https://doi.org/10.1038/srep43042

    Article  CAS  Google Scholar 

  35. Gordon PV (2007) JR Swanson1, JT Attridge1 and R Clark Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell’s criteria? J Perinatol 27(11):661–671

    Article  CAS  Google Scholar 

  36. Pumberger W, Mayr M, Kohlhauser C, Weninger M (2002) Spontaneous localized intestinal perforation in very-low-birth-weight infants: a distinct clinical entity different from necrotizing enterocolitis. J Am Coll Surg 195(6):796–803

    Article  Google Scholar 

  37. Yeung CY, Lee HC, Lin SP, Fang SB, Jiang CB, Huang FY, Chuang CK (2004) Serum cytokines in differentiating between viral and bacterial enterocolitis. Ann Trop Paediatr 24(4):337–343

    Article  Google Scholar 

  38. Iwańczak B, Ruczka M, Matusiewicz M, Pytrus T, Matusiewicz K, Krzesiek E (2020) Correlation between biomarkers (calprotectin, seromucoid, metalloproteinase-3 and CRP) and clinical and endoscopic activity of ulcerative colitis in children. Adv Med Sci 65(2):259–264. https://doi.org/10.1016/j.advms.2020.03.004

    Article  PubMed  Google Scholar 

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Funding

This study is supported by the National Natural Science Foundation of China (Grant Nos. 81571483 and 81971431; Recipient: Jialin Yu), the State Key Clinic Discipline Project (No. 2011-873), and Shenzhen Science and Technology Innovation Free Exploration Project (No. JCYJ20170817100735621).

Author information

Authors and Affiliations

  1. Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Chen Cheng, Yu He, Sa Xiao, Qing Ai & Jialin Yu

  2. Department of Pediatrics, Shenzhen University General Hospital, Shenzhen, Guangdong, People’s Republic of China

    Jialin Yu

  3. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China

    Chen Cheng, Yu He, Sa Xiao, Qing Ai & Jialin Yu

  4. National Clinical Research Center for Child Health and Disorders, Chongqing, People’s Republic of China

    Chen Cheng, Yu He, Sa Xiao, Qing Ai & Jialin Yu

  5. China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing, People’s Republic of China

    Chen Cheng, Yu He, Sa Xiao, Qing Ai & Jialin Yu

  6. Chongqing Key Laboratory of Pediatrics, Chongqing, People’s Republic of China

    Chen Cheng, Yu He, Sa Xiao, Qing Ai & Jialin Yu

Authors
  1. Chen Cheng
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  2. Yu He
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  3. Sa Xiao
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  4. Qing Ai
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  5. Jialin Yu
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Contributions

Chen Cheng was in charge of all works of the study, Yu He helped design the research protocol, Sa Xiao helped to collect the stool specimens, Qing Ai helped to solve some technical problems met during the experiments, and Jialin Yu read and approved the final manuscript.

Corresponding author

Correspondence to Jialin Yu.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the ethics commission of the Children’s Hospital of Chongqing Medical University (Approval Number 108/2013).

Informed consent

Informed consent was obtained from the parents of neonates included in the study.

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Communicated by Daniele De Luca

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Cheng, C., He, Y., Xiao, S. et al. The association between enteric viruses and necrotizing enterocolitis. Eur J Pediatr 180, 225–232 (2021). https://doi.org/10.1007/s00431-020-03746-w

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  • DOI: https://doi.org/10.1007/s00431-020-03746-w

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