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Research Paper

Necrotizing enterocolitis, gut microbes, and sepsis

, , , , , & ORCID Icon show all
Article: 2221470 | Received 25 Dec 2022, Accepted 25 May 2023, Published online: 13 Jun 2023

References

  • Neu J, Walker WA. Necrotizing enterocolitis - review article. N Engl J Med. 2011;364(3):255–21. doi:10.1056/NEJMra1005408.
  • Yazji I, Sodhi CP, Lee EK, Good M, Egan CE, Afrazi A, Neal MD, Jia H, Lin J, Ma C, et al. Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via Enos-NO-nitrite signaling. Proceedings of the National Academy of Sciences of the United States of America. 2013; p. 9451–9456. doi:10.1073/pnas.1219997110.
  • Nino DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 2016;13(10):590–600. doi:10.1038/nrgastro.2016.119.
  • Nolan LS, Wynn JL, Good M. Exploring clinically-relevant experimental models of neonatal shock and necrotizing enterocolitis. Shock. 2020;53(5):596–604. doi:10.1097/SHK.0000000000001507.
  • Holman RC, Stoll BJ, Curns AT, Yorita KL, Steiner CA, Schonberger LB. Necrotising enterocolitis hospitalisations among neonates in the United States. Paediatr Perinat Epidemiol. 2006;20(6):498–506. doi:10.1111/j.1365-3016.2006.00756.x.
  • Pammi M, De Plaen IG, Maheshwari A. Recent advances in necrotizing enterocolitis research: strategies for implementation in clinical practice. Clin Perinatol. 2020;47(2):383–397. doi:10.1016/j.clp.2020.02.011.
  • Samuels N, RA van de Graaf, RCJ de Jonge, Reiss IKM, Vermeulen MJ, van de Graaf RA, de Jonge RCJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr. 2017;17(1). doi:10.1186/s12887-017-0847-3.
  • Cortez AR, Poling HM, Brown NE, Singh A, Mahe MM, Helmrath MA Transplantation of human intestinal organoids into the mouse mesentery: a more physiologic and anatomic engraftment site. Surgery (United States) 2018; 164(4):643–50.
  • Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet. 1990;336(8730):1519–1523. doi:10.1016/0140-6736(90)93304-8.
  • Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants. 2019.
  • Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006;368(9543):1271–1283. doi:10.1016/S0140-6736(06)69525-1.
  • Fitzgibbons SC, Ching Y, Yu D, Carpenter J, Kenny M, Weldon C, Lillehei C, Valim C, Horbar JD, Jaksic T. Mortality of necrotizing enterocolitis expressed by birth weight categories. Journal Of Pediatric Surgery. 2009;44(6):1072–1075. discussion 5-6. doi:10.1016/j.jpedsurg.2009.02.013.
  • Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 2016;13(10):590–600. doi:10.1038/nrgastro.2016.119.
  • Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastro Hepat. 2016;13(10):590–600. doi:10.1038/nrgastro.2016.119.
  • Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, Poole WK, Blakely ML, Wright L, Higgins R, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005;115(3):696–703. doi:10.1542/peds.2004-0569.
  • McNelis K, Goddard G, Jenkins T, Poindexter A, Wessel J, Helmrath M, Poindexter B. Delay in achieving enteral autonomy and growth outcomes in very low birth weight infants with surgical necrotizing enterocolitis. J Perinatol. 2021;41(1):150–156. doi:10.1038/s41372-020-00880-z.
  • Pammi M, Cope J, Tarr PI, Warner BB, Morrow AL, Mai V, Gregory KE, Kroll JS, McMurtry V, Ferris MJ, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome. 2017;5(1). doi:10.1186/s40168-017-0248-8.
  • Kovler ML, Gonzalez Salazar AJ, Fulton WB, Lu P, Yamaguchi Y, Zhou Q, Sampah M, Ishiyama A, Prindle T, Wang S, et al. Toll-like receptor 4–mediated enteric glia loss is critical for the development of necrotizing enterocolitis. Sci Transl Med. 2021;13(612):eabg3459. doi:10.1126/scitranslmed.abg3459.
  • Jilling T, Simon D, Lu J, Meng FJ, Li D, Schy R, Thomson RB, Soliman A, Arditi M, Caplan MS, et al. The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis. The J Immunol. 2006;177(5):3273–3282. doi:10.4049/jimmunol.177.5.3273.
  • Leaphart CL, Cavallo J, Gribar SC, Cetin S, Li J, Branca MF, Dubowski TD, Sodhi CP, Hackam DJ. A critical role for tlr4 in the pathogenesis of necrotizing enterocolitis by modulating intestinal injury and repair. The journal of immunology. 2007;179(7):4808–4820. doi:10.4049/jimmunol.179.7.4808.
  • Garg PM, Paschal JL, Ansari MAY, Block D, Inagaki K, Weitkamp JH. Clinical impact of NEC-associated sepsis on outcomes in preterm infants. Pediatr Res. 2022;92(6):1705–1715. doi:10.1038/s41390-022-02034-7.
  • Masi AC, Stewart CJ. The role of the preterm intestinal microbiome in sepsis and necrotising enterocolitis. Early Hum Dev. 2019;138:104854. doi:10.1016/j.earlhumdev.2019.104854.
  • Parra-Llorca A, Pinilla-Gonzlez A, Torrejon-Rodriguez L, Lara-Canton I, Kuligowski J, Collado MC, Gormaz M, Aguar M, Vento M, Serna E, et al. Effects of sepsis on immune response, microbiome and oxidative metabolism in preterm infants. Children (Basel). 2023;10(3):602. doi:10.3390/children10030602.
  • Chetta KE, Vincent KG, Fanning B, Klumb AB, Chetta JA, Rohrer AM, Spence LH, Hill JG. Impact of delayed time to antibiotics in medical and surgical necrotizing enterocolitis. Children (Basel). 2023;10(1):160. doi:10.3390/children10010160.
  • Madan JC, Salari RC, Saxena D, Davidson L, O’Toole GA, Moore JH, Sogin ML, Foster JA, Edwards WH, Palumbo P, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97(6):F456–62. doi:10.1136/fetalneonatal-2011-301373.
  • Bizzarro MJ, Ehrenkranz RA, Gallagher PG. Concurrent bloodstream infections in infants with necrotizing enterocolitis. J Pediatr Us. 2014;164(1):61–66. doi:10.1016/j.jpeds.2013.09.020.
  • Clyman RI, Jin C, Hills NK. A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis. J Perinatol. 2020;40(11):1662–1670. doi:10.1038/s41372-020-0691-4.
  • Silverman MA, Konnikova L, Gerber JS. Impact of antibiotics on necrotizing enterocolitis and antibiotic-associated diarrhea. Gastroenterol Clin North Am. 2017;46(1):61–76. doi:10.1016/j.gtc.2016.09.010.
  • Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sánchez PJ, Ambalavanan N, Benjamin DK. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics. 2009;123(1):58–66. doi:10.1542/peds.2007-3423.
  • Alexander VN, Northrup V, Bizzarro MJ. Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr. 2011;159(3):392–397. doi:10.1016/j.jpeds.2011.02.035.
  • Chaaban H, Patel MM, Burge K, Eckert JV, Lupu C, Keshari RS, Silasi R, Regmi G, Trammell M, Dyer D, et al. Early antibiotic exposure alters intestinal development and increases susceptibility to necrotizing enterocolitis: a mechanistic study. Microorganisms. 2022;10(3):519. doi:10.3390/microorganisms10030519.
  • Saleem B, Okogbule-Wonodi AC, Fasano A, Magder LS, Ravel J, Kapoor S, Viscardi RM. Intestinal barrier maturation in very low birthweight infants: relationship to feeding and antibiotic exposure. J Pediatr. 2017;183:31–36.e1. doi:10.1016/j.jpeds.2017.01.013.
  • Maayan-Metzger A, Itzchak A, Mazkereth R, Kuint J. Necrotizing enterocolitis in full-term infants: case-control study and review of the literature. J Perinatol. 2004;24(8):494–499. doi:10.1038/sj.jp.7211135.
  • Martinez-Tallo E, Claure N, Bancalari E. Necrotizing enterocolitis in full-term or near-term infants: risk factors. Biol Neonate. 1997;71(5):292–298. doi:10.1159/000244428.
  • Lee JY, Park KH, Kim A, Yang HR, Jung EY, Cho SH. Maternal and placental risk factors for developing necrotizing enterocolitis in very preterm infants. Pediatr Neonatol. 2017;58(1):57–62. doi:10.1016/j.pedneo.2016.01.005.
  • Lambert DK, Christensen RD, Henry E, Besner GE, Baer VL, Wiedmeier SE, Stoddard RA, Miner CA, Burnett J. Necrotizing enterocolitis in term neonates: data from a multihospital health-care system. J Perinatol. 2007;27(7):437–443. doi:10.1038/sj.jp.7211738.
  • Berkhout DJC, Klaassen P, Niemarkt HJ, de Boode WP, Cossey V, van Goudoever JB, Hulzebos C, Andriessen P, van Kaam A, Kramer B, et al. Risk factors for necrotizing enterocolitis: a prospective multicenter case-control study. Neonatology. 2018;114(3):277–284. doi:10.1159/000489677.
  • Sharma R, Tepas JJ, Hudak ML, Mollitt DL, Wludyka PS, Teng RJ, Premachandra BR. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg. 2007;42(3):454–461. doi:10.1016/j.jpedsurg.2006.10.038.
  • Hackam DJ, Sodhi CP. Bench to bedside — new insights into the pathogenesis of necrotizing enterocolitis. Nat Rev Gastro Hepat. 2022;19(7):468–479. doi:10.1038/s41575-022-00594-x.
  • Sharma R, Hudak ML. A clinical perspective of necrotizing enterocolitis: past, present, and future. Clin Perinatol. 2013;40(1):27±. doi:10.1016/j.clp.2012.12.012.
  • Wertheimer F, Arcinue R, Niklas V. Necrotizing enterocolitis: enhancing awareness for the general practitioner. Pediatr Rev. 2019;40(10):517–527. doi:10.1542/pir.2017-0338.
  • Andrews RE, Coe KL. Clinical presentation and multifactorial pathogenesis of necrotizing enterocolitis in the preterm infant. Adv Neonat Care. 2021;21(5):349–355. doi:10.1097/ANC.0000000000000880.
  • Rich BS, Dolgin SE. Necrotizing enterocolitis. Pediatr Rev. 2017;38(12):552–559. doi:10.1542/pir.2017-0002.
  • Patel RM, Ferguson J, McElroy SJ, Khashu M, Caplan MS. Defining necrotizing enterocolitis: current difficulties and future opportunities. Pediatr Res. 2020;88(S1):10–15. doi:10.1038/s41390-020-1074-4.
  • Sampah MES, Hackam DJ. Prenatal immunity and influences on necrotizing enterocolitis and associated neonatal disorders. Front Immunol. 2021;12:650709. doi:10.3389/fimmu.2021.650709.
  • Perez-Munoz ME, Arrieta MC, Ramer-Tait AE, Walter J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017;5(1):48. doi:10.1186/s40168-017-0268-4.
  • Chan KY, Leung KT, Tam YH, Lam HS, Cheung HM, Ma TP, Lee KH, To KF, Li K, Ng PC, et al. Genome-wide expression profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in human intestinal tissues: dysregulation of functional pathways. Ann Surg. 2014;260(6):1128–1137. doi:10.1097/SLA.0000000000000374.
  • Costello EK, Carlisle EM, Bik EM, Morowitz MJ, Relman DA, Blaser MJ. Microbiome assembly across multiple body sites in low-birthweight infants. mBio. 2013;4(6):e00782–13. doi:10.1128/mBio.00782-13.
  • Maheshwari A, Schelonka RL, Dimmitt RA, Carlo WA, Munoz-Hernandez B, Das A, McDonald SA, Thorsen P, Skogstrand K, Hougaard DM, et al. Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants. Pediatr Res. 2014;76(1):100–108. doi:10.1038/pr.2014.48.
  • Sisk PM, Lovelady CA, Dillard RG, Gruber KJ, O’Shea TM. Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants. J Perinatol. 2007;27(7):428–433. doi:10.1038/sj.jp.7211758.
  • Dirix V, Vermeulen F, Mascart F. Maturation of CD4+ regulatory T lymphocytes and of cytokine secretions in infants born prematurely. J Clin Immunol. 2013;33(6):1126–1133. doi:10.1007/s10875-013-9911-4.
  • Alganabi M, Lee C, Bindi E, Li B, Pierro A. Recent advances in understanding necrotizing enterocolitis. F1000 Res. 2019;8:107. doi:10.12688/f1000research.17228.1.
  • Eaton S, Rees CM, Hall NJ. Current research in necrotizing enterocolitis. Early Hum Dev. 2016;97:33–39. doi:10.1016/j.earlhumdev.2016.01.013.
  • Eaton S, Rees CM, Hall NJ. Current research on the epidemiology, pathogenesis, and management of necrotizing enterocolitis. Neonatol. 2017;111(4):423–430. doi:10.1159/000458462.
  • Hackam DJ, Sodhi CP. Bench to bedside — new insights into the pathogenesis of necrotizing enterocolitis. Nat Rev Gastroenterol Hepatol. 2022;19(7):468–479. doi:10.1038/s41575-022-00594-x.
  • Afrazi A, Branca MF, Sodhi CP, Good M, Yamaguchi Y, Egan CE, Lu P, Jia H, Shaffiey S, Lin J, et al. Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis. J Biol Chem. 2014;289(14):9584–9599. doi:10.1074/jbc.M113.526517.
  • Jilling T, Lu J, Jackson M, Caplan MS. Intestinal epithelial apoptosis initiates gross bowel necrosis in an experimental rat model of neonatal necrotizing enterocolitis. Pediatr Res. 2004;55(4):622–629. doi:10.1203/01.PDR.0000113463.70435.74.
  • Liu Y, Fatheree NY, Mangalat N, Rhoads JM. Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-kappaB signaling in the intestine. Am J Physiol Gastrointest Liver Physiol. 2012;302(6):G608–17. doi:10.1152/ajpgi.00266.2011.
  • Maynard AA, Dvorak K, Khailova L, Dobrenen H, Arganbright KM, Halpern MD, Kurundkar AR, Maheshwari A, Dvorak B. Epidermal growth factor reduces autophagy in intestinal epithelium and in the rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G614–22. doi:10.1152/ajpgi.00076.2010.
  • Neal MD, Sodhi CP, Dyer M, Craig BT, Good M, Jia H, Yazji I, Afrazi A, Richardson WM, Beer-Stolz D, et al. A critical role for TLR4 induction of autophagy in the regulation of enterocyte migration and the pathogenesis of necrotizing enterocolitis. J Immunol. 2013;190(7):3541–3551. doi:10.4049/jimmunol.1202264.
  • Werts AD, Fulton WB, Ladd MR, Saad-Eldin A, Chen YX, Kovler ML, Jia H, Banfield EC, Buck RH, Goehring K, et al. A novel role for necroptosis in the pathogenesis of necrotizing enterocolitis. Cell Mol Gastroenterol Hepatol. 2020;9(3):403–423. doi:10.1016/j.jcmgh.2019.11.002.
  • Yu Y, Shiou SR, Guo Y, Lu L, Westerhoff M, Sun J, Petrof EO, Claud EC. Erythropoietin protects epithelial cells from excessive autophagy and apoptosis in experimental neonatal necrotizing enterocolitis. PLos One. 2013;8(7):e69620. doi:10.1371/journal.pone.0069620.
  • Cetin S, Ford HR, Sysko LR, Agarwal C, Wang J, Neal MD, Baty C, Apodaca G, Hackam DJ. Endotoxin inhibits intestinal epithelial restitution through activation of Rho-GTPase and increased focal adhesions. J Biol Chem. 2004;279(23):24592–24600. doi:10.1074/jbc.M313620200.
  • Neal MD, Sodhi CP, Jia H, Dyer M, Egan CE, Yazji I, Good M, Afrazi A, Marino R, Slagle D, et al. Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. J Biol Chem. 2012;287(44):37296–37308. doi:10.1074/jbc.M112.375881.
  • Qureshi FG, Leaphart C, Cetin S, Li J, Grishin A, Watkins S, Ford HR, Hackam DJ. Increased expression and function of integrins in enterocytes by endotoxin impairs epithelial restitution. Gastroenterology. 2005;128(4):1012–1022. doi:10.1053/j.gastro.2005.01.052.
  • Sodhi CP, Shi XH, Richardson WM, Grant ZS, Shapiro RA, Prindle T, Branca M, Russo A, Gribar SC, Ma C, et al. Toll-like receptor-4 inhibits enterocyte proliferation via impaired β-catenin signaling in necrotizing enterocolitis. Gastroenterology. 2010;138(1):185–196. doi:10.1053/j.gastro.2009.09.045.
  • Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60(2):367–389. doi:10.1016/j.pcl.2012.12.003.
  • Denning NL, Prince JM. Neonatal intestinal dysbiosis in necrotizing enterocolitis. Mol Med. 2018;24(1):4. doi:10.1186/s10020-018-0002-0.
  • Dowling DJ, Levy O. Ontogeny of early life immunity. Trends Immunol. 2014;35(7):299–310. doi:10.1016/j.it.2014.04.007.
  • Wynn JL, Neu J, Moldawer LL, Levy O. Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis. J Perinatol. 2009;29(2):79–88. doi:10.1038/jp.2008.132.
  • Melville JM, Moss TJ. The immune consequences of preterm birth. Front Neurosci. 2013;7:79. doi:10.3389/fnins.2013.00079.
  • Clark JA, Doelle SM, Halpern MD, Saunders TA, Holubec H, Dvorak K, Boitano SA, Dvorak B. Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. Am J Physiol Gastrointest Liver Physiol. 2006;291(5):G938–49. doi:10.1152/ajpgi.00090.2006.
  • Salzman NH, Underwood MA, Bevins CL. Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol. 2007;19(2):70–83. doi:10.1016/j.smim.2007.04.002.
  • Starner TD, Agerberth B, Gudmundsson GH, McCray PB. Expression and activity of beta-defensins and LL-37 in the developing human lung. J Immunol. 2005;174(3):1608–1615. doi:10.4049/jimmunol.174.3.1608.
  • Weaver LT, Laker MF, Nelson R. Intestinal permeability in the newborn. Arch Dis Child. 1984;59(3):236–241. doi:10.1136/adc.59.3.236.
  • Carr R, Modi N. Haemopoietic colony stimulating factors for preterm neonates. Arch Dis Child Fetal Neonatal Ed. 1997;76(2):F128–33. doi:10.1136/fn.76.2.F128.
  • Davis CA, Vallota EH, Forristal J. Serum complement levels in infancy: age related changes. Pediatr Res. 1979;13(9):1043–1046. doi:10.1203/00006450-197909000-00019.
  • Johnston RB, Altenburger KM, Atkinson AW, Curry RH. Complement in the newborn infant. Pediatrics. 1979;64(5 Pt 2 Suppl):781–786. doi:10.1542/peds.64.5.781.
  • McGreal EP, Hearne K, Spiller OB. Off to a slow start: under-development of the complement system in term newborns is more substantial following premature birth. Immunobiol. 2012;217(2):176–186. doi:10.1016/j.imbio.2011.07.027.
  • Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi:10.1155/2012/985646.
  • Shen L, Turner JR. Role of epithelial cells in initiation and propagation of intestinal inflammation. Eliminating the static: tight junction dynamics exposed. Am J Physiol Gastrointest Liver Physiol. 2006;290(4):G577–82. doi:10.1152/ajpgi.00439.2005.
  • van den Berg JP, Westerbeek EA, Berbers GA, van Gageldonk PG, van der Klis FR, van Elburg RM, van den Berg JP, van Gageldonk PGM, van der Klis FRM. Transplacental transport of IgG antibodies specific for pertussis, diphtheria, tetanus, Haemophilus influenzae type b, and Neisseria meningitidis serogroup C is lower in preterm compared with term infants. Pediatr Infect Dis J. 2010;29(9):801–805. doi:10.1097/INF.0b013e3181dc4f77.
  • Azizia M, Lloyd J, Allen M, Klein N, Peebles D. Immune status in very preterm neonates. Pediatrics. 2012;129(4):e967–74. doi:10.1542/peds.2011-1579.
  • Marodi L, Goda K, Palicz A, Szabo G. Cytokine receptor signalling in neonatal macrophages: defective STAT-1 phosphorylation in response to stimulation with IFN-gamma. Clin Exp Immunol. 2001;126(3):456–460. doi:10.1046/j.1365-2249.2001.01693.x.
  • Raymond SL, Mathias BJ, Murphy TJ, Rincon JC, Lopez MC, Ungaro R, Ellett F, Jorgensen J, Wynn JL, Baker HV, et al. Neutrophil chemotaxis and transcriptomics in term and preterm neonates. Transl Res. 2017;190:4–15. doi:10.1016/j.trsl.2017.08.003.
  • Idzikowski E, Connors TJ. Impact and clinical implications of prematurity on adaptive immune development. Curr Pediatr Rep. 2020;8(4):194–201. doi:10.1007/s40124-020-00234-5.
  • Hackam DJ, Sodhi CP. Toll-like receptor-mediated intestinal inflammatory imbalance in the pathogenesis of necrotizing enterocolitis. Cell Mol Gastroenterol Hepatol. 2018;6(2):229–38 e1. doi:10.1016/j.jcmgh.2018.04.001.
  • Vincent D, Klinke M, Eschenburg G, Trochimiuk M, Appl B, Tiemann B, Bergholz R, Reinshagen K, Boettcher M. NEC is likely a NETs dependent process and markers of NETosis are predictive of NEC in mice and humans. Sci Rep. 2018;8(1):12612. doi:10.1038/s41598-018-31087-0.
  • Klinke M, Chaaban H, Boettcher M. The role of neutrophil extracellular traps in necrotizing enterocolitis. Front Pediatr. 2023;11:1121193. doi:10.3389/fped.2023.1121193.
  • Yost CC, Cody MJ, Harris ES, Thornton NL, McInturff AM, Martinez ML, Chandler NB, Rodesch CK, Albertine KH, Petti CA, et al. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood. 2009;113(25):6419–6427. doi:10.1182/blood-2008-07-171629.
  • Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO, Ruan Y. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5(7):e177. doi:10.1371/journal.pbio.0050177.
  • Rodriguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, Avershina E, Rudi K, Narbad A, Jenmalm MC, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050. doi:10.3402/mehd.v26.26050.
  • Stewart CJ, Ajami NJ, O’Brien JL, Hutchinson DS, Smith DP, Wong MC, Ross MC, Lloyd RE, Doddapaneni H, Metcalf GA, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562(7728):583–588. doi:10.1038/s41586-018-0617-x.
  • Stewart CJ, Embleton ND, Marrs EC, Smith DP, Nelson A, Abdulkadir B, Skeath T, Petrosino JF, Perry JD, Berrington JE, et al. Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease. Microbiome. 2016;4(1):67. doi:10.1186/s40168-016-0216-8.
  • Stewart CJ, Embleton ND, Marrs ECL, Smith DP, Fofanova T, Nelson A, Skeath T, Perry JD, Petrosino JF, Berrington JE, et al. Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome. 2017;5(1):75. doi:10.1186/s40168-017-0295-1.
  • De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019;195(1):74–85. doi:10.1111/cei.13158.
  • Pascal M, Perez-Gordo M, Caballero T, Escribese MM, Lopez Longo MN, Luengo O, Manso L, Matheu V, Seoane E, Zamorano M, et al. Microbiome and allergic diseases. Front Immunol. 2018;9:1584. doi:10.3389/fimmu.2018.01584.
  • Schlechte J, Skalosky I, Geuking MB, McDonald B. Long-distance relationships - regulation of systemic host defense against infections by the gut microbiota. Mucosal Immunol. 2022;15(5):809–818. doi:10.1038/s41385-022-00539-2.
  • Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020;30(6):492–506. doi:10.1038/s41422-020-0332-7.
  • Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, Andoh A. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol. 2018;11(1):1–10. doi:10.1007/s12328-017-0813-5.
  • Shen ZH, Zhu CX, Quan YS, Yang ZY, Wu S, Luo WW, Tan B, Wang X-Y. Relationship between intestinal microbiota and ulcerative colitis: mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. 2018;24(1):5–14. doi:10.3748/wjg.v24.i1.5.
  • Dickson RP, Schultz MJ, van der Poll T, Schouten LR, Falkowski NR, Luth JE, Sjoding MW, Brown CA, Chanderraj R, Huffnagle GB, et al. Lung microbiota predict clinical outcomes in critically ill patients. Am J Respir Crit Care Med. 2020;201(5):555–563. doi:10.1164/rccm.201907-1487OC.
  • Kullberg RFJ, Hugenholtz F, Brands X, Kinsella CM, Peters-Sengers H, Butler JM, Deijs M, Klein M, Faber DR, Scicluna BP, et al. Rectal bacteriome and virome signatures and clinical outcomes in community-acquired pneumonia: an exploratory study. EClinical Med. 2021;39:101074. doi:10.1016/j.eclinm.2021.101074.
  • Lamarche D, Johnstone J, Zytaruk N, Clarke F, Hand L, Loukov D, Szamosi JC, Rossi L, Schenck LP, Verschoor CP, et al. Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study. Respir Res. 2018;19(1):245. doi:10.1186/s12931-018-0950-5.
  • Bozzetti V, Senger S. Organoid technologies for the study of intestinal microbiota-host interactions. Trends Mol Med. 2022;28(4):290–303. doi:10.1016/j.molmed.2022.02.001.
  • Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55–71. doi:10.1038/s41579-020-0433-9.
  • Hendrikx T, Schnabl B. Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation. J Intern Med. 2019;286(1):32–40. doi:10.1111/joim.12892.
  • Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219–232. doi:10.1038/nri.2017.7.
  • Kelleher SL, Alam S, Rivera OC, Barber-Zucker S, Zarivach R, Wagatsuma T, Kambe T, Soybel DI, Wright J, Lamendella R, et al. Loss-of-function SLC30A2 mutants are associated with gut dysbiosis and alterations in intestinal gene expression in preterm infants. Gut Microbes. 2022;14(1):2014739. doi:10.1080/19490976.2021.2014739.
  • Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65. doi:10.1126/scitranslmed.3008599.
  • Ardissone AN, de la Cruz DM, Davis-Richardson AG, Rechcigl KT, Li N, Drew JC, Murgas-Torrazza R, Sharma R, Hudak ML, Triplett EW, et al. Meconium microbiome analysis identifies bacteria correlated with premature birth. PLos One. 2014;9(3):e90784. doi:10.1371/journal.pone.0090784.
  • Vinturache AE, Gyamfi-Bannerman C, Hwang J, Mysorekar IU, Jacobsson B. Preterm birth international C. Maternal microbiome - a pathway to preterm birth. Semin Fetal Neonatal Med. 2016;21(2):94–99. doi:10.1016/j.siny.2016.02.004.
  • Thanert R, Keen EC, Dantas G, Warner BB, Tarr PI. Necrotizing enterocolitis and the microbiome: current status and future directions. J Infect Dis. 2021;223(12 Suppl 2):S257–S63. doi:10.1093/infdis/jiaa604.
  • Younge NE, Newgard CB, Cotten CM, Goldberg RN, Muehlbauer MJ, Bain JR, Stevens RD, O’Connell TM, Rawls JF, Seed PC, et al. Disrupted maturation of the microbiota and metabolome among extremely preterm infants with postnatal growth failure. Sci Rep. 2019;9(1):8167. doi:10.1038/s41598-019-44547-y.
  • Claud EC, Keegan KP, Brulc JM, Lu L, Bartels D, Glass E, Chang EB, Meyer F, Antonopoulos DA. Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants. Microbiome. 2013;1(1):20. doi:10.1186/2049-2618-1-20.
  • Mai V, Young CM, Ukhanova M, Wang X, Sun Y, Casella G, Theriaque D, Li N, Sharma R, Hudak M, et al. Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLos One. 2011;6(6):e20647. doi:10.1371/journal.pone.0020647.
  • Neu J. Necrotizing enterocolitis: a multi-omic approach and the role of the microbiome. Dig Dis Sci. 2020;65(3):789–796. doi:10.1007/s10620-020-06104-w.
  • Pammi M, Cope J, Tarr PI, Warner BB, Morrow AL, Mai V, Gregory KE, Kroll JS, McMurtry V, Ferris MJ, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome. 2017;5(1):31. doi:10.1186/s40168-017-0248-8.
  • Warner BB, Deych E, Zhou Y, Hall-Moore C, Weinstock GM, Sodergren E, Shaikh N, Hoffmann JA, Linneman LA, Hamvas A, et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 2016;387(10031):1928–1936. doi:10.1016/S0140-6736(16)00081-7.
  • Arboleya S, Sanchez B, Milani C, Duranti S, Solis G, Fernandez N, de Los Reyes-Gavilán CG, Ventura M, Margolles A, Gueimonde M, et al. Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics. J Pediatr. 2015;166(3):538–544. doi:10.1016/j.jpeds.2014.09.041.
  • Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD neonatal research network. Pediatr. 2002;110(2):285–291. doi:10.1542/peds.110.2.285.
  • Mai V, Torrazza RM, Ukhanova M, Wang X, Sun Y, Li N, Shuster J, Sharma R, Hudak ML, Neu J, et al. Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants. PLos One. 2013;8(1):e52876. doi:10.1371/journal.pone.0052876.
  • Shaw AG, Sim K, Randell P, Cox MJ, McClure ZE, Li MS, Donaldson H, Langford PR, Cookson WOCM, Moffatt MF, et al. Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants. PLos One. 2015;10(7):e0132923. doi:10.1371/journal.pone.0132923.
  • Taft DH, Ambalavanan N, Schibler KR, Yu Z, Newburg DS, Deshmukh H, Ward DV, Morrow AL. Center variation in intestinal microbiota prior to late-onset sepsis in preterm infants. PLos One. 2015;10(6):e0130604. doi:10.1371/journal.pone.0130604.
  • Askie LM, Darlow BA, Davis PG, Finer N, Stenson B, Vento M, Whyte R. Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Cochrane Database Syst Rev. 2017;4(2). CD011190. doi:10.1002/14651858.CD011190.pub2.
  • Askie LM, Darlow BA, Finer N, Schmidt B, Stenson B, Tarnow-Mordi W, Davis PG, Carlo WA, Brocklehurst P, Davies LC, et al. Association between oxygen saturation targeting and death or disability in extremely preterm infants in the neonatal oxygenation prospective meta-analysis collaboration. JAMA. 2018;319(21):2190–2201. doi:10.1001/jama.2018.5725.
  • Yazji I, Sodhi CP, Lee EK, Good M, Egan CE, Afrazi A, Neal MD, Jia H, Lin J, Ma C, et al. Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via Enos–NO–nitrite signaling. Proc Natl Acad Sci U S A. 2013;110(23):9451–9456. doi:10.1073/pnas.1219997110.
  • Yan X, Managlia E, Liu SX, Tan XD, Wang X, Marek C, De Plaen IG. Lack of VEGFR2 signaling causes maldevelopment of the intestinal microvasculature and facilitates necrotizing enterocolitis in neonatal mice. Am J Physiol Gastrointest Liver Physiol. 2016;310(9):G716–25. doi:10.1152/ajpgi.00273.2015.
  • Bowker RM, Yan X, De Plaen IG. Intestinal microcirculation and necrotizing enterocolitis: the vascular endothelial growth factor system. Semin Fetal Neonatal Med. 2018;23(6):411–415. doi:10.1016/j.siny.2018.08.008.
  • Chen Y, Chang KT, Lian DW, Lu H, Roy S, Laksmi NK, Low Y, Krishnaswamy G, Pierro A, Ong CCP, et al. The role of ischemia in necrotizing enterocolitis. J Pediatr Surg. 2016;51(8):1255–1261. doi:10.1016/j.jpedsurg.2015.12.015.
  • Moore SA, Nighot P, Reyes C, Rawat M, McKee J, Lemon D, Hanson J, Ma TY. Intestinal barrier dysfunction in human necrotizing enterocolitis. J Pediatr Surg. 2016;51(12):1907–1913. doi:10.1016/j.jpedsurg.2016.09.011.
  • Good M, Siggers RH, Sodhi CP, Afrazi A, Alkhudari F, Egan CE, Neal MD, Yazji I, Jia H, Lin J, et al. Amniotic fluid inhibits toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium. Proc Natl Acad Sci U S A. 2012;109(28):11330–11335. doi:10.1073/pnas.1200856109.
  • Yu QH, Yang Q. Diversity of tight junctions (TJs) between gastrointestinal epithelial cells and their function in maintaining the mucosal barrier. Cell Biol Int. 2009;33(1):78–82. doi:10.1016/j.cellbi.2008.09.007.
  • Bein A, Eventov-Friedman S, Arbell D, Schwartz B. Intestinal tight junctions are severely altered in NEC preterm neonates. Pediatr Neonatol. 2018;59(5):464–473. doi:10.1016/j.pedneo.2017.11.018.
  • Liu D, Xu Y, Feng J, Yu J, Huang J, Li Z. Mucins and tight junctions are severely altered in necrotizing enterocolitis neonates. Am J Perinatol. 2021;38(11):1174–1180. doi:10.1055/s-0040-1710558.
  • Yu Y, Lu L, Sun J, Petrof EO, Claud EC. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model. Am J Physiol Gastrointest Liver Physiol. 2016;311(3):G521–32. doi:10.1152/ajpgi.00022.2016.
  • Dai S, Sodhi C, Cetin S, Richardson W, Branca M, Neal MD, Prindle T, Ma C, Shapiro RA, Li B, et al. Extracellular high mobility group box-1 (HMGB1) inhibits enterocyte migration via activation of toll-like receptor-4 and increased cell-matrix adhesiveness. J Biol Chem. 2010;285(7):4995–5002. doi:10.1074/jbc.M109.067454.
  • Hansen CH, Krych Ł, Buschard K, Metzdorff SB, Nellemann C, Hansen LH, Nielsen DS, Frøkiær H, Skov S, Hansen AK, et al. A maternal gluten-free diet reduces inflammation and diabetes incidence in the offspring of NOD mice. Diabetes. 2014;63(8):2821–2832. doi:10.2337/db13-1612.
  • Neu J. Developmental aspects of maternal-fetal, and infant gut microbiota and implications for long-term health. Matern Health Neonatol Perinatol. 2015;1(1):6. doi:10.1186/s40748-015-0007-4.
  • de Aguero M G, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, Steinert A, Heikenwalder M, Hapfelmeier S, Sauer U, et al. The maternal microbiota drives early postnatal innate immune development. Science. 2016;351(6279):1296–1302. doi:10.1126/science.aad2571.
  • Rothhammer V, Quintana FJ. The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat Rev Immunol. 2019;19(3):184–197. doi:10.1038/s41577-019-0125-8.
  • Lu P, Yamaguchi Y, Fulton WB, Wang S, Zhou Q, Jia H, Kovler ML, Salazar AG, Sampah M, Prindle T, et al. Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis. Nat Commun. 2021;12(1):1042. doi:10.1038/s41467-021-21356-4.
  • Pan X, Zhang D, Nguyen DN, Wei W, Yu X, Gao F, Sangild PT. Postnatal gut immunity and microbiota development is minimally affected by prenatal inflammation in preterm pigs. Front Immunol. 2020;11:420. doi:10.3389/fimmu.2020.00420.
  • Elgin TG, Fricke EM, Gong H, Reese J, Mills DA, Kalantera KM, Underwood MA, McElroy SJ. Fetal exposure to maternal inflammation interrupts murine intestinal development and increases susceptibility to neonatal intestinal injury. Dis Model Mech. 2019;12(10). doi:10.1242/dmm.040808.
  • Watson SN, McElroy SJ. Potential prenatal origins of necrotizing enterocolitis. Gastroenterol Clin North Am. 2021;50(2):431–444. doi:10.1016/j.gtc.2021.02.006.
  • Miller J, Tonkin E, Damarell RA, McPhee AJ, Suganuma M, Suganuma H, Middleton P, Makrides M, Collins C. A systematic review and meta-analysis of human milk feeding and morbidity in very low birth weight infants. Nutrients. 2018;10(6):707. doi:10.3390/nu10060707.
  • Sodhi CP, Wipf P, Yamaguchi Y, Fulton WB, Kovler M, Nino DF, Zhou Q, Banfield E, Werts AD, Ladd MR, et al. The human milk oligosaccharides 2’-fucosyllactose and 6’-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr Res. 2021;89(1):91–101. doi:10.1038/s41390-020-0852-3.
  • Gnoth MJ, Kunz C, Kinne-Saffran E, Rudloff S. Human milk oligosaccharides are minimally digested in vitro. J Nutr. 2000;130(12):3014–3020. doi:10.1093/jn/130.12.3014.
  • Xu G, Davis JC, Goonatilleke E, Smilowitz JT, German JB, Lebrilla CB. Absolute quantitation of human milk oligosaccharides reveals phenotypic variations during lactation. J Nutr. 2017;147(1):117–124. doi:10.3945/jn.116.238279.
  • Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL. Breast milk oligosaccharides: structure-function relationships in the neonate. Annu Rev Nutr. 2014;34(1):143–169. doi:10.1146/annurev-nutr-071813-105721.
  • Sahin S, Ozdemir T, Katipoglu N, Akcan AB, Kaynak Turkmen M. Comparison of changes in breast milk macronutrient content during the first month in preterm and term infants. Breastfeed Med. 2020;15(1):56–62. doi:10.1089/bfm.2019.0141.
  • Conze DB, Kruger CL, Symonds JM, Lodder R, Schönknecht YB, Ho M, Derya SM, Parkot J, Parschat K. Weighted analysis of 2′-fucosyllactose, 3-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose concentrations in human milk. Food Chem Toxicol. 2022;163:112877. doi:10.1016/j.fct.2022.112877.
  • Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491–502. doi:10.1038/nrgastro.2017.75.
  • Rousseaux A, Brosseau C, Le Gall S, Piloquet H, Barbarot S, Bodinier M. Human milk oligosaccharides: their effects on the host and their potential as therapeutic agents. Front Immunol. 2021;12:680911. doi:10.3389/fimmu.2021.680911.
  • Coppa GV, Gabrielli O, Zampini L, Galeazzi T, Ficcadenti A, Padella L, Santoro L, Soldi S, Carlucci A, Bertino E, et al. Oligosaccharides in 4 different milk groups, Bifidobacteria, and Ruminococcus obeum. J Pediatr Gastroenterol Nutr. 2011;53(1):80–87. doi:10.1097/MPG.0b013e3182073103.
  • Morrow AL, Ruiz-Palacios GM, Altaye M, Jiang X, Guerrero ML, Meinzen-Derr JK, Farkas T, Chaturvedi P, Pickering LK, Newburg DS, et al. Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. J Pediatr. 2004;145(3):297–303. doi:10.1016/j.jpeds.2004.04.054.
  • Bode L, Kunz C, Muhly-Reinholz M, Mayer K, Seeger W, Rudloff S. Inhibition of monocyte, lymphocyte, and neutrophil adhesion to endothelial cells by human milk oligosaccharides. Thromb Haemost. 2004;92(6):1402–1410. doi:10.1160/TH04-01-0055.
  • Torres Roldan VD, Urtecho SM, Gupta J, Yonemitsu C, Carcamo CP, Bode L, Ochoa TJ. Human milk oligosaccharides and their association with late-onset neonatal sepsis in Peruvian very-low-birth-weight infants. Am J Clin Nutr. 2020;112(1):106–112. doi:10.1093/ajcn/nqaa102.
  • Wang C, Zhang M, Guo H, Yan J, Liu F, Chen J, Li Y, Ren F. Human milk oligosaccharides protect against necrotizing enterocolitis by inhibiting intestinal damage via increasing the proliferation of crypt cells. Mol Nutr Food Res. 2019;63(18):e1900262. doi:10.1002/mnfr.201900262.
  • Goehring KC, Marriage BJ, Oliver JS, Wilder JA, Barrett EG, Buck RH. Similar to those who are breastfed, infants fed a formula containing 2’-fucosyllactose have lower inflammatory cytokines in a randomized controlled trial. J Nutr. 2016;146(12):2559–2566. doi:10.3945/jn.116.236919.
  • He Y, Liu S, Kling DE, Leone S, Lawlor NT, Huang Y, Feinberg SB, Hill DR, Newburg DS. The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation. Gut. 2016;65(1):33–46. doi:10.1136/gutjnl-2014-307544.
  • Puccio G, Alliet P, Cajozzo C, Janssens E, Corsello G, Sprenger N, Wernimont S, Egli D, Gosoniu L, Steenhout P, et al. Effects of infant formula with human milk oligosaccharides on growth and morbidity: a randomized multicenter trial. J Pediatr Gastroenterol Nutr. 2017;64(4):624–631. doi:10.1097/MPG.0000000000001520.
  • Sodhi CP, Wipf P, Yamaguchi Y, Fulton WB, Kovler M, Niño DF, Zhou Q, Banfield E, Werts AD, Ladd MR, et al. The human milk oligosaccharides 2’-fucosyllactose and 6’-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr Res. 2021;89(1):91–101. doi:10.1038/s41390-020-0852-3.
  • Jantscher-Krenn E, Zherebtsov M, Nissan C, Goth K, Guner YS, Naidu N, Choudhury B, Grishin AV, Ford HR, Bode L, et al. The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. Gut. 2012;61(10):1417–1425. doi:10.1136/gutjnl-2011-301404.
  • Autran CA, Kellman BP, Kim JH, Asztalos E, Blood AB, Spence ECH, Patel AL, Hou J, Lewis NE, Bode L, et al. Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants. Gut. 2018;67(6):1064–1070. doi:10.1136/gutjnl-2016-312819.
  • Autran CA, Schoterman MH, Jantscher-Krenn E, Kamerling JP, Bode L. Sialylated galacto-oligosaccharides and 2’-fucosyllactose reduce necrotising enterocolitis in neonatal rats. Br J Nutr. 2016;116(2):294–299. doi:10.1017/S0007114516002038.
  • Bergstrom KS, Xia L. Mucin-type O-glycans and their roles in intestinal homeostasis. Glycobiology. 2013;23(9):1026–1037. doi:10.1093/glycob/cwt045.
  • Wu RY, Li B, Koike Y, Maattanen P, Miyake H, Cadete M, Johnson‐Henry KC, Botts SR, Lee C, Abrahamsson TR, et al. Human milk oligosaccharides increase mucin expression in experimental necrotizing enterocolitis. Mol Nutr Food Res. 2019;63(3):e1800658. doi:10.1002/mnfr.201800658.
  • Holscher HD, Davis SR, Tappenden KA. Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe and HT-29 cell lines. J Nutr. 2014;144(5):586–591. doi:10.3945/jn.113.189704.
  • Perdijk O, van Baarlen P, Fernandez-Gutierrez MM, van den Brink E, Schuren FHJ, Brugman S, Savelkoul HFJ, Kleerebezem M, van Neerven RJJ. Corrigendum: sialyllactose and galactooligosaccharides promote epithelial barrier functioning and distinctly modulate microbiota composition and short chain fatty acid production in vitro. Front Immunol. 2019;10:762. doi:10.3389/fimmu.2019.00762.
  • Perdijk O, van Baarlen P, Fernandez-Gutierrez MM, van den Brink E, Schuren FHJ, Brugman S, Savelkoul HFJ, Kleerebezem M, van Neerven RJJ. Sialyllactose and galactooligosaccharides promote epithelial barrier functioning and distinctly modulate microbiota composition and short chain fatty acid production in vitro. Front Immunol. 2019;10:94. doi:10.3389/fimmu.2019.00094.
  • Chi C, Li C, Buys N, Wang W, Yin C, Sun J. Effects of probiotics in preterm infants: a network meta-analysis. Pediatr. 2021;147(1). doi:10.1542/peds.2020-0706.
  • Morgan RL, Preidis GA, Kashyap PC, Weizman AV, Sadeghirad B, Chang Y, Florez ID, Foroutan F, Shahid S, Zeraatkar D, et al. Probiotics reduce mortality and morbidity in preterm, low-birth-weight infants: a systematic review and network meta-analysis of randomized trials. Gastroenterology. 2020;159(2):467–480. doi:10.1053/j.gastro.2020.05.096.
  • Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2020;10(10). CD005496. doi:10.1002/14651858.CD005496.pub5.
  • AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2014;2014(4). CD005496. doi:10.1002/14651858.CD005496.pub4.
  • Good M, Sodhi CP, Ozolek JA, Buck RH, Goehring KC, Thomas DL, Vikram A, Bibby K, Morowitz MJ, Firek B, et al. Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets: evidence in mice for a role of TLR9. Am J Physiol Gastrointest Liver Physiol. 2014;306(11):G1021–32. doi:10.1152/ajpgi.00452.2013.
  • Gribar SC, Sodhi CP, Richardson WM, Anand RJ, Gittes GK, Branca MF, Jakub A, Shi X-H, Shah S, Ozolek JA, et al. Reciprocal expression and signaling of TLR4 and TLR9 in the pathogenesis and treatment of necrotizing enterocolitis. J Immunol. 2009;182(1):636–646. doi:10.4049/jimmunol.182.1.636.
  • Liu Y, Tian X, He B, Hoang TK, Taylor CM, Blanchard E, Freeborn J, Park S, Luo M, Couturier J, et al. Lactobacillus reuteri DSM 17938 feeding of healthy newborn mice regulates immune responses while modulating gut microbiota and boosting beneficial metabolites. Am J Physiol Gastrointest Liver Physiol. 2019;317(6):G824–G38. doi:10.1152/ajpgi.00107.2019.
  • Guo S, Gillingham T, Guo Y, Meng D, Zhu W, Walker WA, Ganguli K. Secretions of Bifidobacterium infantis and Lactobacillus acidophilus protect intestinal epithelial barrier function. J Pediatr Gastroenterol Nutr. 2017;64(3):404–412. doi:10.1097/MPG.0000000000001310.
  • Underwood MA. Probiotics and the prevention of necrotizing enterocolitis. J Pediatr Surg. 2019;54(3):405–412. doi:10.1016/j.jpedsurg.2018.08.055.
  • Filler R, Li B, Chusilp S, Pierro A. Amniotic fluid and breast milk: a rationale for breast milk stem cell therapy in neonatal diseases. Pediatr Surg Int. 2020;36(9):999–1007. doi:10.1007/s00383-020-04710-3.
  • Melnik BC, Stremmel W, Weiskirchen R, John SM, Schmitz G. Exosome-derived microRNAs of human milk and their effects on infant health and development. Biomolecules. 2021;11(6):851. doi:10.3390/biom11060851.
  • He S, Liu G, Zhu X. Human breast milk-derived exosomes may help maintain intestinal epithelial barrier integrity. Pediatr Res. 2021;90(2):366–372. doi:10.1038/s41390-021-01449-y.
  • Vaishnavi C. Translocation of gut flora and its role in sepsis. Indian J Med Microbiol. 2013;31(4):334–342. doi:10.4103/0255-0857.118870.
  • Gill EM, Jung K, Qvist N, Ellebaek MB. Antibiotics in the medical and surgical treatment of necrotizing enterocolitis. A systematic review. BMC Pediatr. 2022;22(1):66. doi:10.1186/s12887-022-03120-9.
  • Bury RG, Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. Cochrane Database Syst Rev. 2001;2001(1). CD000405. doi:10.1002/14651858.CD000405.
  • Cuna A, Morowitz MJ, Sampath V. Early antibiotics and risk for necrotizing enterocolitis in premature infants: a narrative review. Front Pediatr. 2023;11:1112812. doi:10.3389/fped.2023.1112812.
  • Birck MM, Nguyen DN, Cilieborg MS, Kamal SS, Nielsen DS, Damborg P, Olsen JE, Lauridsen C, Sangild PT, Thymann T, et al. Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs. Am J Physiol Gastrointest Liver Physiol. 2016;310(5):G323–33. doi:10.1152/ajpgi.00392.2015.
  • Nguyen DN, Fuglsang E, Jiang P, Birck MM, Pan X, Kamal SB, Pors SE, Gammelgaard PL, Nielsen DS, Thymann T, et al. Oral antibiotics increase blood neutrophil maturation and reduce bacteremia and necrotizing enterocolitis in the immediate postnatal period of preterm pigs. Innate Immun. 2016;22(1):51–62. doi:10.1177/1753425915615195.
  • Dierikx TH, Deianova N, Groen J, Vijlbrief DC, Hulzebos C, de Boode WP, d’Haens EJ, Cossey V, Kramer BW, van Weissenbruch MM, et al. Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study. Eur J Pediatr. 2022;181(10):3715–3724. doi:10.1007/s00431-022-04579-5.
  • Ting JY, Roberts A, Sherlock R, Ojah C, Cieslak Z, Dunn M, Barrington K, Yoon EW, Shah PS. Duration of initial empirical antibiotic therapy and outcomes in very low birth weight infants. Pediatrics. 2019;143(3). doi:10.1542/peds.2018-2286.
  • Shah D, Sinn JK. Antibiotic regimens for the empirical treatment of newborn infants with necrotising enterocolitis. Cochrane Database Syst Rev. 2012;2012(8):CD007448. doi:10.1002/14651858.CD007448.pub2.
  • Petrosyan M, Guner YS, Williams M, Grishin A, Ford HR. Current concepts regarding the pathogenesis of necrotizing enterocolitis. Pediatr Surg Int. 2009;25(4):309–318. doi:10.1007/s00383-009-2344-8.
  • Gill EM, Jung K, Qvist N, Elleb MB. Antibiotics in the medical and surgical treatment of necrotizing enterocolitis. A systematic review. BMC Pediatr. 2022;22(1). doi:10.1186/s12887-022-03120-9.
  • Papillon S, Castle SL, Gayer CP, Ford HR. Necrotizing enterocolitis: contemporary management and outcomes. Adv Pediatr. 2013;60(1):263–279. doi:10.1016/j.yapd.2013.04.011.
  • Neu J. Necrotizing enterocolitis. World Rev Nutr Diet. 2014;110:253–263.
  • Luig M, Lui K, Nsw, Group AN. Epidemiology of necrotizing enterocolitis–part II: risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005;41(4):174–179. doi:10.1111/j.1440-1754.2005.00583.x.
  • Holman RC, Stoll BJ, Clarke MJ, Glass RI. The epidemiology of necrotizing enterocolitis infant mortality in the United States. Am J Public Health. 1997;87(12):2026–2031. doi:10.2105/AJPH.87.12.2026.
  • Downard CD, Renaud E, St Peter SD, Abdullah F, Islam S, Saito JM, Blakely ML, Huang EY, Arca MJ, Cassidy L, et al. Treatment of necrotizing enterocolitis: an American pediatric surgical association outcomes and clinical trials committee systematic review. J Pediatr Surg. 2012;47(11):2111–2122. doi:10.1016/j.jpedsurg.2012.08.011.
  • Kastenberg ZJ, Sylvester KG. The surgical management of necrotizing enterocolitis. Clin Perinatol. 2013;40(1):135–148. doi:10.1016/j.clp.2012.12.011.
  • Dukleska K, Devin CL, Martin AE, Miller JM, Sullivan KM, Levy C, Prestowitz S, Flathers K, Vinocur CD, Berman L, et al. Necrotizing enterocolitis totalis: high mortality in the absence of an aggressive surgical approach. Surgery. 2019;165(6):1176–1181. doi:10.1016/j.surg.2019.03.005.
  • Patel EU, Wilson DA, Brennan EA, Lesher AP, Ryan RM. Earlier re-initiation of enteral feeding after necrotizing enterocolitis decreases recurrence or stricture: a systematic review and meta-analysis. J Perinatol. 2020;40(11):1679–1687. doi:10.1038/s41372-020-0722-1.
  • Jiang P, Trimigno A, Stanstrup J, Khakimov B, Viereck N, Engelsen SB, Sangild PT, Dragsted LO. Antibiotic treatment preventing necrotising enterocolitis alters urinary and plasma metabolomes in preterm pigs. J Proteome Res. 2017;16(10):3547–3557. doi:10.1021/acs.jproteome.7b00263.
  • Raba AA, O’Sullivan A, Miletin J. Pathogenesis of necrotising enterocolitis: the impact of the altered gut microbiota and antibiotic exposure in preterm infants. Acta Paediatr. 2021;110(2):433–440. doi:10.1111/apa.15559.
  • Roberts JL, Patel RM. Antibiotic utilisation in very low birth weight infants without sepsis or necrotising enterocolitis is associated with multiple adverse outcomes. Evid Based Med. 2017;22(5):187. doi:10.1136/ebmed-2017-110756.
  • Scheifele DW, Ginter GL, Olsen E, Fussell S, Pendray M. Comparison of two antibiotic regimens for neonatal necrotizing enterocolitis. J Antimicrob Chemother. 1987;20(3):421–429. doi:10.1093/jac/20.3.421.
  • Zangari A, Noviello C, Nobile S, Cobellis G, Gulia C, Piergentili R, Gigli S, Carnielli V. Surgical management of necrotizing enterocolitis in an incredibly low birth weight infant and review of the literature. Clin Ter. 2017;168(5):e297–e9. doi:10.7417/T.2017.2024.
  • Heida FH, Loos MH, Stolwijk L, Te Kiefte BJ, van den Ende SJ, Onland W, van Rijn RR, Dikkers R, van den Dungen FAM, Kooi EMW, et al. Risk factors associated with postnecrotizing enterocolitis strictures in infants. J Pediatr Surg. 2016;51(7):1126–1130. doi:10.1016/j.jpedsurg.2015.09.015.
  • Amin SC, Pappas C, Iyengar H, Maheshwari A. Short bowel syndrome in the NICU. Clin Perinatol. 2013;40(1):53–68. doi:10.1016/j.clp.2012.12.003.
  • Sparks EA, Khan FA, Fisher JG, Fullerton BS, Hall A, Raphael BP, Duggan C, Modi BP, Jaksic T. Necrotizing enterocolitis is associated with earlier achievement of enteral autonomy in children with short bowel syndrome. J Pediatr Surg. 2016;51(1):92–95. doi:10.1016/j.jpedsurg.2015.10.023.
  • Soraisham AS, Amin HJ, Al-Hindi MY, Singhal N, Sauve RS. Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight ≤1250 g? J Paediatr Child Health. 2006;42(9):499–504. doi:10.1111/j.1440-1754.2006.00910.x.
  • Dilli D, Eras Z, Özkan Ulu H, Dilmen U, Durgut Şakrucu E. Does necrotizing enterocolitis affect growth and neurodevelopmental outcome in very low birth weight infants? Pediatr Surg Int. 2012;28(5):471–476. doi:10.1007/s00383-012-3051-4.
  • Sonntag J, Grimmer I, Scholz T, Metze B, Wit J, Obladen M. Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis. Acta Paediatr. 2000;89(5):528–532. doi:10.1111/j.1651-2227.2000.tb00332.x.
  • Schulzke SM, Deshpande GC, Patole SK. Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing enterocolitis: a systematic review of observational studies. Arch Pediatr Adolesc Med. 2007;161(6):583–590. doi:10.1001/archpedi.161.6.583.
  • Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007;92(3):F193–8. doi:10.1136/adc.2006.099929.
  • Shah TA, Meinzen-Derr J, Gratton T, Steichen J, Donovan EF, Yolton K, Alexander B, Narendran V, Schibler KR. Hospital and neurodevelopmental outcomes of extremely low-birth-weight infants with necrotizing enterocolitis and spontaneous intestinal perforation. J Perinatol. 2012;32(7):552–558. doi:10.1038/jp.2011.176.
  • Zozaya C, Shah J, Pierro A, Zani A, Synnes A, Lee S, Shah PS. Neurodevelopmental and growth outcomes of extremely preterm infants with necrotizing enterocolitis or spontaneous intestinal perforation. J Pediatr Surg. 2021;56(2):309–316. doi:10.1016/j.jpedsurg.2020.05.013.
  • Chen S, Xiao X, Lin S, Zhu J, Liang L, Zhu M, Yang Z, Chen S, Lin Z, Liu Y, et al. Early aEEG can predict neurodevelopmental outcomes at 12 to 18 month of age in VLBWI with necrotizing enterocolitis: a cohort study. BMC Pediatr. 2021;21(1):582. doi:10.1186/s12887-021-03056-6.