{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:51:48Z","timestamp":1790049108688,"version":"4.0.1"},"reference-count":115,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s10020-018-0002-0","type":"journal-article","created":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T08:10:20Z","timestamp":1521015020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Neonatal intestinal dysbiosis in necrotizing enterocolitis"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6444-3845","authenticated-orcid":false,"given":"Naomi-Liza","family":"Denning","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Prince","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"2_CR1","first-page":"237ra265","volume":"6","author":"K Aagaard","year":"2014","unstructured":"Aagaard K, et al. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6:237ra265.","journal-title":"Sci Transl Med"},{"key":"2_CR2","doi-asserted-by":"publisher","first-page":"521","DOI":"10.5144\/0256-4947.2012.521","volume":"32","author":"EA Abdel Ghany","year":"2012","unstructured":"Abdel Ghany EA, Ali AA. Empirical antibiotic treatment and the risk of necrotizing enterocolitis and death in very low birth weight neonates. Ann Saudi Med. 2012;32:521\u20136.","journal-title":"Ann Saudi Med"},{"key":"2_CR3","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1177\/0009922809349161","volume":"49","author":"F Abdullah","year":"2010","unstructured":"Abdullah F, et al. Necrotizing enterocolitis in 20,822 infants: analysis of medical and surgical treatments. Clin Pediatr (Phila). 2010;49:166\u201371.","journal-title":"Clin Pediatr (Phila)"},{"key":"2_CR4","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1651-2227.2008.01060.x","volume":"98","author":"I Adlerberth","year":"2009","unstructured":"Adlerberth I, Wold AE. Establishment of the gut microbiota in western infants. Acta Paediatr. 2009;98:229\u201338.","journal-title":"Acta Paediatr"},{"key":"2_CR5","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.jpeds.2011.02.035","volume":"159","author":"VN Alexander","year":"2011","unstructured":"Alexander VN, Northrup V, Bizzarro MJ. Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr. 2011;159:392\u20137.","journal-title":"J Pediatr"},{"key":"2_CR6","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1097\/01.shk.0000239774.02904.65","volume":"27","author":"RJ Anand","year":"2007","unstructured":"Anand RJ, Leaphart CL, Mollen KP, Hackam DJ. The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis. Shock. 2007;27:124\u201333.","journal-title":"Shock"},{"key":"2_CR7","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.anaerobe.2012.04.013","volume":"18","author":"S Arboleya","year":"2012","unstructured":"Arboleya S, et al. Deep 16S rRNA metagenomics and quantitative PCR analyses of the premature infant fecal microbiota. Anaerobe. 2012;18:378\u201380.","journal-title":"Anaerobe"},{"key":"2_CR8","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1111\/j.1574-6941.2011.01261.x","volume":"79","author":"S Arboleya","year":"2017","unstructured":"Arboleya S, et al. Establishment and development of intestinal microbiota in preterm neonates. FEMS Microbiol Ecol. 2017;79:763\u201372.","journal-title":"FEMS Microbiol Ecol"},{"key":"2_CR9","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.anaerobe.2011.03.009","volume":"17","author":"E Bezirtzoglou","year":"2011","unstructured":"Bezirtzoglou E, Tsiotsias A, Welling GW. Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH). Anaerobe. 2011;17:478\u201382.","journal-title":"Anaerobe"},{"key":"2_CR10","doi-asserted-by":"publisher","first-page":"1796s","DOI":"10.1093\/jn\/138.9.1796S","volume":"138","author":"G Biasucci","year":"2008","unstructured":"Biasucci G, Benenati B, Morelli L, Bessi E, Boehm G. Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr. 2008;138:1796s\u2013800s.","journal-title":"J Nutr"},{"key":"2_CR11","first-page":"191","volume":"8","author":"LJ Brandt","year":"2012","unstructured":"Brandt LJ. Fecal transplantation for the treatment of Clostridium Difficile infection. Gastroenterol Hepatol (N Y). 2012;8:191\u20134.","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"2_CR12","doi-asserted-by":"publisher","first-page":"544","DOI":"10.3945\/ajcn.112.037382","volume":"96","author":"R Cabrera-Rubio","year":"2012","unstructured":"Cabrera-Rubio R, et al. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012;96:544\u201351.","journal-title":"Am J Clin Nutr"},{"key":"2_CR13","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.pcl.2012.12.003","volume":"60","author":"A Camacho-Gonzalez","year":"2013","unstructured":"Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin N Am. 2013;60:367\u201389.","journal-title":"Pediatr Clin N Am"},{"key":"2_CR14","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1053\/j.sempedsurg.2005.05.002","volume":"14","author":"MS Caplan","year":"2005","unstructured":"Caplan MS, Simon D, Jilling T. The role of PAF, TLR, and the inflammatory response in neonatal necrotizing enterocolitis. Semin Pediatr Surg. 2005;14:145\u201351.","journal-title":"Semin Pediatr Surg"},{"key":"2_CR15","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1097\/01.ANC.0000338019.56405.29","volume":"8","author":"BM Carter","year":"2008","unstructured":"Carter BM, Holditch-Davis D. Risk factors for NEC in preterm infants: how race, gender and health status contribute. Adv Neonatal Care. 2008;8:285\u201390.","journal-title":"Adv Neonatal Care"},{"key":"2_CR16","doi-asserted-by":"publisher","first-page":"7404","DOI":"10.1073\/pnas.0401710101","volume":"101","author":"EC Claud","year":"2004","unstructured":"Claud EC, et al. Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc Natl Acad Sci U S A. 2004;101:7404\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2_CR17","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S0140-6736(15)01027-2","volume":"387","author":"K Costeloe","year":"2016","unstructured":"Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet. 2016;387:649\u201360.","journal-title":"Lancet"},{"key":"2_CR18","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1542\/peds.2007-3423","volume":"123","author":"CM Cotten","year":"2009","unstructured":"Cotten CM, et al. 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;123:58\u201366.","journal-title":"Pediatrics"},{"key":"2_CR19","doi-asserted-by":"publisher","first-page":"e0158136","DOI":"10.1371\/journal.pone.0158136","volume":"11","author":"LA Denkel","year":"2016","unstructured":"Denkel LA, et al. Protective effect of dual-strain probiotics in preterm infants: a multi-center time series analysis. PLoS One. 2016;11:e0158136.","journal-title":"PLoS One"},{"key":"2_CR20","doi-asserted-by":"publisher","first-page":"1131s","DOI":"10.1093\/ajcn\/73.6.1131S","volume":"73","author":"B Deplancke","year":"2001","unstructured":"Deplancke B, Gaskins HR. Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. Am J Clin Nutr. 2001;73:1131s\u201341s.","journal-title":"Am J Clin Nutr"},{"key":"2_CR21","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.siny.2011.10.001","volume":"17","author":"DB DiGiulio","year":"2012","unstructured":"DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med. 2012;17:2\u201311.","journal-title":"Semin Fetal Neonatal Med"},{"key":"2_CR22","doi-asserted-by":"publisher","unstructured":"Dogra S, et al. Dynamics of infant gut microbiota are influenced by delivery mode and gestational duration and are associated with subsequent adiposity. MBio. 2015;6(1):414-19. https:\/\/doi.org\/10.1128\/mBio.02419-14 .","DOI":"10.1128\/mBio.02419-14"},{"key":"2_CR23","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1053\/j.gastro.2011.02.011","volume":"140","author":"MG Dominguez-Bello","year":"2011","unstructured":"Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology. 2011;140:1713\u20139.","journal-title":"Gastroenterology"},{"key":"2_CR24","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/nm.4039","volume":"22","author":"MG Dominguez-Bello","year":"2016","unstructured":"Dominguez-Bello MG, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016;22:250\u20133.","journal-title":"Nat Med"},{"key":"2_CR25","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.crvi.2016.04.008","volume":"339","author":"SD Ehrlich","year":"2016","unstructured":"Ehrlich SD. The human gut microbiome impacts health and disease. C R Biol. 2016;339:319\u201323.","journal-title":"C R Biol"},{"key":"2_CR26","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/j.clinthera.2016.01.005","volume":"38","author":"TG Elgin","year":"2016","unstructured":"Elgin TG, Kern SL, McElroy SJ. Development of the neonatal intestinal microbiome and its association with necrotizing enterocolitis. Clin Ther. 2016;38:706\u201315.","journal-title":"Clin Ther"},{"key":"2_CR27","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1093\/jac\/dkx088","volume":"72","author":"E Esaiassen","year":"2017","unstructured":"Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis. J Antimicrob Chemother. 2017;72:1858\u201370.","journal-title":"J Antimicrob Chemother"},{"key":"2_CR28","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.niox.2017.03.003","volume":"66","author":"E Ferretti","year":"2017","unstructured":"Ferretti E, et al. The nitric oxide synthase 2 pathway is targeted by both pro- and anti-inflammatory treatments in the immature human intestine. Nitric Oxide. 2017;66:53\u201361.","journal-title":"Nitric Oxide"},{"key":"2_CR29","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/j.jpedsurg.2009.02.013","volume":"44","author":"SC Fitzgibbons","year":"2009","unstructured":"Fitzgibbons SC, et al. Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg. 2009;44:1072\u20135. discussion 1075-1076.","journal-title":"J Pediatr Surg"},{"key":"2_CR30","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1053\/j.sempedsurg.2013.01.005","volume":"22","author":"BL Frost","year":"2013","unstructured":"Frost BL, Caplan MS. Necrotizing enterocolitis: pathophysiology, platelet-activating factor, and probiotics. Semin Pediatr Surg. 2013;22:88\u201393.","journal-title":"Semin Pediatr Surg"},{"key":"2_CR31","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/S0022-2275(20)36953-4","volume":"34","author":"M Furukawa","year":"1993","unstructured":"Furukawa M, Narahara H, Yasuda K, Johnston JM. Presence of platelet-activating factor-acetylhydrolase in milk. J Lipid Res. 1993;34:1603\u20139.","journal-title":"J Lipid Res"},{"key":"2_CR32","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1038\/mi.2015.30","volume":"8","author":"M Good","year":"2015","unstructured":"Good M, et al. Breast milk protects against the development of necrotizing enterocolitis through inhibition of toll-like receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor. Mucosal Immunol. 2015;8:1166\u201379.","journal-title":"Mucosal Immunol"},{"key":"2_CR33","doi-asserted-by":"publisher","first-page":"636","DOI":"10.4049\/jimmunol.182.1.636","volume":"182","author":"SC Gribar","year":"2009","unstructured":"Gribar SC, et al. Reciprocal expression and signaling of TLR4 and TLR9 in the pathogenesis and treatment of necrotizing enterocolitis. J Immunol. 2009;182:636\u201346.","journal-title":"J Immunol"},{"key":"2_CR34","first-page":"17","volume":"3","author":"EC Gritz","year":"2015","unstructured":"Gritz EC, Bhandari V. The human neonatal gut microbiome: a brief review. Front Pediatr. 2015;3:17.","journal-title":"Front Pediatr"},{"key":"2_CR35","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1097\/MPG.0b013e318282a8c2","volume":"56","author":"RW Gupta","year":"2013","unstructured":"Gupta RW, et al. Histamine-2 receptor blockers alter the fecal microbiota in premature infants. J Pediatr Gastroenterol Nutr. 2013;56:397\u2013400.","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2_CR36","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/sj.jp.7210892","volume":"23","author":"SO Guthrie","year":"2003","unstructured":"Guthrie SO, et al. Necrotizing enterocolitis among neonates in the United States. J Perinatol. 2003;23:278\u201385.","journal-title":"J Perinatol"},{"key":"2_CR37","doi-asserted-by":"publisher","first-page":"475415","DOI":"10.1155\/2013\/475415","volume":"2013","author":"DJ Hackam","year":"2013","unstructured":"Hackam DJ, Afrazi A, Good M, Sodhi CP. Innate immune signaling in the pathogenesis of necrotizing enterocolitis. Clin Dev Immunol. 2013;2013:475415.","journal-title":"Clin Dev Immunol"},{"key":"2_CR38","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s11938-014-0042-7","volume":"13","author":"JJ Hansen","year":"2015","unstructured":"Hansen JJ, Sartor RB. Therapeutic manipulation of the microbiome in IBD: current results and future approaches. Curr Treat Options Gastroenterol. 2015;13:105\u201320.","journal-title":"Curr Treat Options Gastroenterol"},{"key":"2_CR39","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1016\/j.jpedsurg.2016.12.022","volume":"52","author":"LW Hansen","year":"2017","unstructured":"Hansen LW, et al. Deficiency in milk fat globule-epidermal growth factor-factor 8 exacerbates organ injury and mortality in neonatal sepsis. J Pediatr Surg. 2017a;52:1520\u20137.","journal-title":"J Pediatr Surg"},{"key":"2_CR40","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.surg.2017.02.006","volume":"162","author":"LW Hansen","year":"2017","unstructured":"Hansen LW, et al. Treatment with milk fat globule epidermal growth factor-factor 8 (MFG-E8) reduces inflammation and lung injury in neonatal sepsis. Surgery. 2017b;162:349\u201357.","journal-title":"Surgery"},{"key":"2_CR41","doi-asserted-by":"publisher","first-page":"e0133320","DOI":"10.1371\/journal.pone.0133320","volume":"10","author":"R Hansen","year":"2015","unstructured":"Hansen R, et al. First-pass meconium samples from healthy term vaginally-delivered neonates: an analysis of the microbiota. PLoS One. 2015;10:e0133320.","journal-title":"PLoS One"},{"key":"2_CR42","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3945\/an.115.010090","volume":"7","author":"Y He","year":"2016","unstructured":"He Y, Lawlor NT, Newburg DS. Human milk components modulate toll-like receptor-mediated inflammation. Adv Nutr. 2016;7:102\u201311.","journal-title":"Adv Nutr"},{"key":"2_CR43","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1126\/science.1058709","volume":"292","author":"LV Hooper","year":"2001","unstructured":"Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science. 2001;292:1115\u20138.","journal-title":"Science"},{"key":"2_CR44","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.humic.2016.09.002","volume":"4","author":"M Hosny","year":"2017","unstructured":"Hosny M. Updating on gut microbiota and its relationship with the occurrence of necrotizing enterocolitis - ScienceDirect. Hum Microbiome J. 2017;4:14\u20139.","journal-title":"Hum Microbiome J"},{"key":"2_CR45","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1136\/archdischild-2011-301141","volume":"97","author":"SY Huh","year":"2012","unstructured":"Huh SY, et al. Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study. Arch Dis Child. 2012;97:610\u20136.","journal-title":"Arch Dis Child"},{"key":"2_CR46","doi-asserted-by":"publisher","first-page":"e6077","DOI":"10.1097\/MD.0000000000006077","volume":"96","author":"L Hui","year":"2017","unstructured":"Hui L, et al. Immunoregulation effects of different gammadeltaT cells and toll-like receptor signaling pathways in neonatal necrotizing enterocolitis. Medicine (Baltimore). 2017;96:e6077.","journal-title":"Medicine (Baltimore)"},{"key":"2_CR47","doi-asserted-by":"publisher","unstructured":"Jayasinghe TN, Chiavaroli V, Holland DJ, Cutfield WS, O\u2019Sullivan JM. The new era of treatment for obesity and metabolic disorders: evidence and expectations for gut microbiome transplantation. Front Cell Infect Microbiol. 2016;6:15. https:\/\/doi.org\/10.3389\/fcimb.2016.00015 .","DOI":"10.3389\/fcimb.2016.00015"},{"key":"2_CR48","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/s00284-005-0020-3","volume":"51","author":"E Jimenez","year":"2005","unstructured":"Jimenez E, et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol. 2005;51:270\u20134.","journal-title":"Curr Microbiol"},{"key":"2_CR49","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.resmic.2007.12.007","volume":"159","author":"E Jimenez","year":"2008","unstructured":"Jimenez E, et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159:187\u201393.","journal-title":"Res Microbiol"},{"key":"2_CR50","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.jpeds.2011.05.033","volume":"159","author":"VS Kuppala","year":"2011","unstructured":"Kuppala VS, Meinzen-Derr J, Morrow AL, Schibler KR. Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants. J Pediatr. 2011;159:720\u20135.","journal-title":"J Pediatr"},{"key":"2_CR51","doi-asserted-by":"publisher","first-page":"12522","DOI":"10.1073\/pnas.1409497111","volume":"111","author":"PS La Rosa","year":"2014","unstructured":"La Rosa PS, et al. Patterned progression of bacterial populations in the premature infant gut. Proc Natl Acad Sci U S A. 2014;111:12522\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2_CR52","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1017\/S0954422410000065","volume":"23","author":"I Le Huerou-Luron","year":"2010","unstructured":"Le Huerou-Luron I, Blat S, Boudry G. Breast- v. Formula-feeding: impacts on the digestive tract and immediate and long-term health effects. Nutr Res Rev. 2010;23:23\u201336.","journal-title":"Nutr Res Rev"},{"key":"2_CR53","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1007\/s00535-015-1082-z","volume":"50","author":"CY Lu","year":"2015","unstructured":"Lu CY, Ni YH. Gut microbiota and the development of pediatric diseases. J Gastroenterol. 2015;50:720\u20136.","journal-title":"J Gastroenterol"},{"key":"2_CR54","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.pathophys.2013.11.007","volume":"21","author":"P Lu","year":"2014","unstructured":"Lu P, Sodhi CP, Hackam DJ. Toll-like receptor regulation of intestinal development and inflammation in the pathogenesis of necrotizing enterocolitis. Pathophysiology. 2014;21:81\u201393.","journal-title":"Pathophysiology"},{"key":"2_CR55","doi-asserted-by":"publisher","first-page":"G917","DOI":"10.1152\/ajpgi.00422.2013","volume":"306","author":"P Lu","year":"2014","unstructured":"Lu P, et al. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol. 2014;306:G917\u201328.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2_CR56","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1016\/0140-6736(90)93304-8","volume":"336","author":"A Lucas","year":"1990","unstructured":"Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet. 1990;336:1519\u201323.","journal-title":"Lancet"},{"key":"2_CR57","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1097\/MOP.0b013e32835a1ac8","volume":"24","author":"JC Madan","year":"2012","unstructured":"Madan JC, Farzan SF, Hibberd PL, Karagas MR. Normal neonatal microbiome variation in relation to environmental factors, infection and allergy. Curr Opin Pediatr. 2012;24:753\u20139.","journal-title":"Curr Opin Pediatr"},{"key":"2_CR58","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1053\/j.gastro.2010.09.043","volume":"140","author":"A Maheshwari","year":"2011","unstructured":"Maheshwari A, et al. TGF-\u03b22 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine. Gastroenterology. 2011;140:242\u201353.","journal-title":"Gastroenterology"},{"key":"2_CR59","doi-asserted-by":"publisher","first-page":"e20647","DOI":"10.1371\/journal.pone.0020647","volume":"6","author":"V Mai","year":"2011","unstructured":"Mai V, et al. Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLoS One. 2011;6:e20647.","journal-title":"PLoS One"},{"key":"2_CR60","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1097\/01.shk.0000192126.33823.87","volume":"25","author":"TA Markel","year":"2006","unstructured":"Markel TA, et al. Cytokines in necrotizing enterocolitis. Shock. 2006;25:329\u201337.","journal-title":"Shock"},{"key":"2_CR61","doi-asserted-by":"crossref","unstructured":"McElroy SJ. Unraveling the enigma that is neonatal necrotizing enterocolitis. J Perinatol. United States. 2014;8:729\u201330.","DOI":"10.1038\/jp.2014.155"},{"key":"2_CR62","doi-asserted-by":"publisher","unstructured":"Melville JM, Moss TJM. The immune consequences of preterm birth. Front Neurosci. 2013;7:79. https:\/\/doi.org\/10.3389\/fnins.2013.00079 .","DOI":"10.3389\/fnins.2013.00079"},{"key":"2_CR63","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.addr.2016.04.032","volume":"105","author":"M Mimee","year":"2016","unstructured":"Mimee M, Citorik RJ, Lu TK. Microbiome therapeutics - advances and challenges. Adv Drug Deliv Rev. 2016;105:44\u201354.","journal-title":"Adv Drug Deliv Rev"},{"key":"2_CR64","volume-title":"Healthcare cost and utilization project (HCUP) statistical briefs","author":"K Mistry","year":"2006","unstructured":"Mistry K, Fingar KR, Elixhauser A. Variation in the rate of cesarean section across U.S. hospitals, 2013: statistical brief #211. In: Healthcare cost and utilization project (HCUP) statistical briefs. Rockville: Agency for Healthcare Research and Quality (US); 2006."},{"key":"2_CR65","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/pr.2016.18","volume":"79","author":"K MohanKumar","year":"2016","unstructured":"MohanKumar K, et al. Smad7 interrupts TGF-beta signaling in intestinal macrophages and promotes inflammatory activation of these cells during necrotizing enterocolitis. Pediatr Res. 2016;79:951\u201361.","journal-title":"Pediatr Res"},{"key":"2_CR66","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1016\/j.jpedsurg.2016.09.011","volume":"51","author":"SA Moore","year":"2016","unstructured":"Moore SA, et al. Intestinal barrier dysfunction in human necrotizing enterocolitis. J Pediatr Surg. 2016;51:1907\u201313.","journal-title":"J Pediatr Surg"},{"key":"2_CR67","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/2049-2618-1-13","volume":"1","author":"AL Morrow","year":"2013","unstructured":"Morrow AL, et al. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants. Microbiome. 2013;1:13.","journal-title":"Microbiome"},{"key":"2_CR68","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1093\/nutrit\/nuw069","volume":"75","author":"A Moya-Perez","year":"2017","unstructured":"Moya-Perez A, et al. Intervention strategies for cesarean section-induced alterations in the microbiota-gut-brain axis. Nutr Rev. 2017;75:225\u201340.","journal-title":"Nutr Rev"},{"issue":"Suppl 1","key":"2_CR69","doi-asserted-by":"publisher","first-page":"S29","DOI":"10.1038\/jp.2010.172","volume":"31","author":"R Murgas Torrazza","year":"2011","unstructured":"Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol. 2011;31(Suppl 1):S29\u201334.","journal-title":"J Perinatol"},{"key":"2_CR70","doi-asserted-by":"publisher","first-page":"S59","DOI":"10.1590\/S0021-75572005000200008","volume":"81","author":"MM Mussi-Pinhata","year":"2005","unstructured":"Mussi-Pinhata MM, Rego MA. Immunological peculiarities of extremely preterm infants: a challenge for the prevention of nosocomial sepsis. J Pediatr. 2005;81:S59\u201368.","journal-title":"J Pediatr"},{"key":"2_CR71","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.3389\/fmicb.2016.01997","volume":"7","author":"R Nagpal","year":"2016","unstructured":"Nagpal R, et al. Sensitive quantitative analysis of the meconium bacterial microbiota in healthy term infants born vaginally or by cesarean section. Front Microbiol. 2016;7:1997.","journal-title":"Front Microbiol"},{"key":"2_CR72","doi-asserted-by":"publisher","first-page":"e17776","DOI":"10.1371\/journal.pone.0017776","volume":"6","author":"N Nanthakumar","year":"2011","unstructured":"Nanthakumar N, et al. The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS One. 2011;6:e17776.","journal-title":"PLoS One"},{"key":"2_CR73","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.4049\/jimmunol.176.5.3070","volume":"176","author":"MD Neal","year":"2006","unstructured":"Neal MD, et al. Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J Immunol. 2006;176:3070\u20139.","journal-title":"J Immunol"},{"key":"2_CR74","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/00054725-200403000-00015","volume":"10","author":"AS Neish","year":"2004","unstructured":"Neish AS. Molecular aspects of intestinal epithelial cell-bacterial interactions that determine the development of intestinal inflammation. Inflamm Bowel Dis. 2004;10:159\u201368.","journal-title":"Inflamm Bowel Dis"},{"key":"2_CR75","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1126\/science.289.5484.1560","volume":"289","author":"AS Neish","year":"2000","unstructured":"Neish AS, et al. Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science. 2000;289:1560\u20133.","journal-title":"Science"},{"key":"2_CR76","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1053\/j.semperi.2016.09.015","volume":"41","author":"J Neu","year":"2017","unstructured":"Neu J, Pammi M. Pathogenesis of NEC: impact of an altered intestinal microbiome. Semin Perinatol. 2017;41:29\u201335.","journal-title":"Semin Perinatol"},{"key":"2_CR77","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1056\/NEJMra1005408","volume":"364","author":"J Neu","year":"2011","unstructured":"Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364:255\u201364.","journal-title":"N Engl J Med"},{"key":"2_CR78","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/nrgastro.2016.119","volume":"13","author":"DF Nino","year":"2016","unstructured":"Nino DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 2016;13:590\u2013600.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2_CR79","doi-asserted-by":"publisher","first-page":"e177","DOI":"10.1371\/journal.pbio.0050177","volume":"5","author":"C Palmer","year":"2007","unstructured":"Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177.","journal-title":"PLoS Biol"},{"key":"2_CR80","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40168-017-0248-8","volume":"5","author":"M Pammi","year":"2017","unstructured":"Pammi M, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome. 2017;5:31.","journal-title":"Microbiome"},{"key":"2_CR81","first-page":"263","volume":"60","author":"S Papillon","year":"2013","unstructured":"Papillon S, Castle SL, Gayer CP, Ford HR. Necrotizing enterocolitis: contemporary management and outcomes. Adv Pediatr Infect Dis. 2013;60:263\u201379.","journal-title":"Adv Pediatr Infect Dis"},{"key":"2_CR82","first-page":"345","volume":"43","author":"HK Park","year":"2005","unstructured":"Park HK, et al. Molecular analysis of colonized bacteria in a human newborn infant gut. J Microbiol. 2005;43:345\u201353.","journal-title":"J Microbiol"},{"key":"2_CR83","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.clp.2017.05.004","volume":"44","author":"AL Patel","year":"2017","unstructured":"Patel AL, Panagos PG, Silvestri JM. Reducing incidence of necrotizing enterocolitis. Clin Perinatol. 2017;44:683\u2013700.","journal-title":"Clin Perinatol"},{"key":"2_CR84","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/pr.2015.97","volume":"78","author":"RM Patel","year":"2015","unstructured":"Patel RM, Denning PW. Intestinal microbiota and its relationship with necrotizing enterocolitis. Pediatr Res. 2015;78:232\u20138.","journal-title":"Pediatr Res"},{"key":"2_CR85","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.femsle.2004.11.052","volume":"243","author":"J Penders","year":"2005","unstructured":"Penders J, et al. Quantification of Bifidobacterium spp., Escherichia Coli and Clostridium Difficile in faecal samples of breast-fed and formula-fed infants by real-time PCR. FEMS Microbiol Lett. 2005;243:141\u20137.","journal-title":"FEMS Microbiol Lett"},{"key":"2_CR86","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.jaci.2008.05.007","volume":"122","author":"M Pistiner","year":"2008","unstructured":"Pistiner M, Gold DR, Abdulkerim H, Hoffman E, Celedon JC. Birth by cesarean section, allergic rhinitis, and allergic sensitization among children with a parental history of atopy. J Allergy Clin Immunol. 2008;122:274\u20139.","journal-title":"J Allergy Clin Immunol"},{"key":"2_CR87","doi-asserted-by":"crossref","unstructured":"Rabinowitz SS et al. (2001) Platelet-activating factor in infants at risk for necrotizing enterocolitis. 2001;138(1):81-86. PubMed - NCBI.","DOI":"10.1067\/mpd.2001.110132"},{"key":"2_CR88","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1097\/MPG.0000000000000523","volume":"59","author":"KW Reisinger","year":"2014","unstructured":"Reisinger KW, et al. Breast-feeding improves gut maturation compared with formula feeding in preterm babies. J Pediatr Gastroenterol Nutr. 2014;59:720\u20134.","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2_CR89","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1007\/s10620-017-4533-y","volume":"62","author":"H Ren","year":"2017","unstructured":"Ren H, Han J, Li Z, Xiong Z. Stem cell factor\/kit signal insufficiency contributes to hypoxia-induced intestinal motility dysfunctions in neonatal mice. Dig Dis Sci. 2017;62:1193\u2013203.","journal-title":"Dig Dis Sci"},{"key":"2_CR90","doi-asserted-by":"publisher","first-page":"28","DOI":"10.5056\/jnm.2011.17.1.28","volume":"17","author":"SH Rhee","year":"2011","unstructured":"Rhee SH. Basic and translational understandings of microbial recognition by toll-like receptors in the intestine. J Neurogastroenterol Motil. 2011;17:28\u201334.","journal-title":"J Neurogastroenterol Motil"},{"key":"2_CR91","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1002\/ebch.1977","volume":"9","author":"J Robinson","year":"2014","unstructured":"Robinson J. Cochrane in context: probiotics for prevention of necrotizing enterocolitis in preterm infants. Evid Based Child Health. 2014;9:672\u20134.","journal-title":"Evid Based Child Health"},{"key":"2_CR92","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1099\/mic.0.043224-0","volume":"156","author":"LC Roger","year":"2010","unstructured":"Roger LC, Costabile A, Holland DT, Hoyles L, McCartney AL. Examination of faecal Bifidobacterium populations in breast- and formula-fed infants during the first 18 months of life. Microbiology. 2010;156:3329\u201341.","journal-title":"Microbiology"},{"key":"2_CR93","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.earlhumdev.2016.05.010","volume":"99","author":"A Romaine","year":"2016","unstructured":"Romaine A, et al. Safety of histamine-2 receptor blockers in hospitalized VLBW infants. Early Hum Dev. 2016;99:27\u201330.","journal-title":"Early Hum Dev"},{"key":"2_CR94","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nri2515","volume":"9","author":"JL Round","year":"2009","unstructured":"Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9:313\u201323.","journal-title":"Nat Rev Immunol"},{"key":"2_CR95","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12887-017-0847-3","volume":"17","author":"N Samuels","year":"2017","unstructured":"Samuels N, van de Graaf RA, de Jonge RCJ, Reiss IKM, Vermeulen MJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr. 2017;17:105.","journal-title":"BMC Pediatr"},{"key":"2_CR96","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1542\/peds.55.3.376","volume":"55","author":"TV Santulli","year":"1975","unstructured":"Santulli TV, et al. Acute necrotizing enterocolitis in infancy: a review of 64 cases. Pediatrics. 1975;55:376\u201387.","journal-title":"Pediatrics"},{"key":"2_CR97","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1203\/01.PDR.0000078274.74607.7A","volume":"54","author":"A Schwiertz","year":"2003","unstructured":"Schwiertz A, et al. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. Pediatr Res. 2003;54:393\u20139.","journal-title":"Pediatr Res"},{"key":"2_CR98","doi-asserted-by":"publisher","first-page":"e92","DOI":"10.1542\/peds.2014-0596","volume":"135","author":"A Sevelsted","year":"2015","unstructured":"Sevelsted A, Stokholm J, Bonnelykke K, Bisgaard H. Cesarean section and chronic immune disorders. Pediatrics. 2015;135:e92\u20138.","journal-title":"Pediatrics"},{"key":"2_CR99","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.jpedsurg.2006.10.038","volume":"42","author":"R Sharma","year":"2007","unstructured":"Sharma R, et al. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg. 2007;42:454\u201361.","journal-title":"J Pediatr Surg"},{"key":"2_CR100","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/MOG.0000000000000139","volume":"31","author":"AB Shreiner","year":"2015","unstructured":"Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;31:69\u201375.","journal-title":"Curr Opin Gastroenterol"},{"key":"2_CR101","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1053\/j.gastro.2009.09.045","volume":"138","author":"CP Sodhi","year":"2010","unstructured":"Sodhi CP, et al. Toll-like receptor-4 inhibits enterocyte proliferation via impaired beta-catenin signaling in necrotizing enterocolitis. Gastroenterology. 2010;138:185\u201396.","journal-title":"Gastroenterology"},{"key":"2_CR102","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/MOG.0b013e328324f857","volume":"25","author":"ME Spehlmann","year":"2009","unstructured":"Spehlmann ME, Eckmann L. Nuclear factor-kappa B in intestinal protection and destruction. Curr Opin Gastroenterol. 2009;25:92\u20139.","journal-title":"Curr Opin Gastroenterol"},{"key":"2_CR103","doi-asserted-by":"publisher","first-page":"e1190","DOI":"10.1542\/peds.2014-1058","volume":"135","author":"A Stey","year":"2015","unstructured":"Stey A, et al. Outcomes and costs of surgical treatments of necrotizing enterocolitis. Pediatrics. 2015;135:e1190\u20137.","journal-title":"Pediatrics"},{"key":"2_CR104","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.jpeds.2009.10.040","volume":"156","author":"S Sullivan","year":"2010","unstructured":"Sullivan S, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010;156:562\u2013567.e561.","journal-title":"J Pediatr"},{"key":"2_CR105","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.1128\/AEM.03910-12","volume":"79","author":"GW Tannock","year":"2013","unstructured":"Tannock GW, et al. Comparison of the compositions of the stool microbiotas of infants fed goat milk formula, cow milk-based formula, or breast milk. Appl Environ Microbiol. 2013;79:3040\u20138.","journal-title":"Appl Environ Microbiol"},{"key":"2_CR106","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1111\/j.1365-2222.2007.02780.x","volume":"38","author":"S Thavagnanam","year":"2008","unstructured":"Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR. A meta-analysis of the association between caesarean section and childhood asthma. Clin Exp Allergy. 2008;38:629\u201333.","journal-title":"Clin Exp Allergy"},{"key":"2_CR107","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.clp.2012.12.009","volume":"40","author":"RM Torrazza","year":"2013","unstructured":"Torrazza RM, Neu J. The altered gut microbiome and necrotizing enterocolitis. Clin Perinatol. 2013;40:93\u2013108.","journal-title":"Clin Perinatol"},{"key":"2_CR108","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.clp.2017.01.005","volume":"44","author":"MA Underwood","year":"2017","unstructured":"Underwood MA, Sohn K. The microbiota of the extremely preterm infant. Clin Perinatol. 2017;44:407\u201327.","journal-title":"Clin Perinatol"},{"issue":"Suppl 1","key":"2_CR109","doi-asserted-by":"publisher","first-page":"S38","DOI":"10.1111\/j.1753-4887.2012.00493.x","volume":"70","author":"LK Ursell","year":"2012","unstructured":"Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the human microbiome. Nutr Rev. 2012;70(Suppl 1):S38\u201344.","journal-title":"Nutr Rev"},{"key":"2_CR110","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.clinthera.2016.01.006","volume":"38","author":"K Vongbhavit","year":"2016","unstructured":"Vongbhavit K, Underwood MA. Prevention of necrotizing enterocolitis through manipulation of the intestinal microbiota of the premature infant. Clin Ther. 2016;38:716\u201332.","journal-title":"Clin Ther"},{"key":"2_CR111","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/jp.2013.128","volume":"34","author":"R Wadhawan","year":"2014","unstructured":"Wadhawan R, et al. Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous intestinal perforation or surgical necrotizing enterocolitis. J Perinatol. 2014;34:64\u201370.","journal-title":"J Perinatol"},{"key":"2_CR112","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/ismej.2009.37","volume":"3","author":"Y Wang","year":"2009","unstructured":"Wang Y, et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J. 2009;3:944\u201354.","journal-title":"ISME J"},{"key":"2_CR113","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1053\/j.sempedsurg.2013.01.004","volume":"22","author":"DJ Watkins","year":"2013","unstructured":"Watkins DJ, Besner GE. The role of the intestinal microcirculation in necrotizing enterocolitis. Semin Pediatr Surg. 2013;22:83\u20137.","journal-title":"Semin Pediatr Surg"},{"key":"2_CR114","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/jp.2008.132","volume":"29","author":"JL Wynn","year":"2009","unstructured":"Wynn JL, Neu J, Moldawer LL, Levy O. Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis. J Perinatol. 2009;29:79\u201388.","journal-title":"J Perinatol"},{"key":"2_CR115","doi-asserted-by":"crossref","unstructured":"Xing T, Camacho Salazar R, Chen YH. Animal models for studying epithelial barriers in neonatal necrotizing enterocolitis, inflammatory bowel disease and colorectal cancer. Tissue Barriers. 2017;5(4):e1356901.","DOI":"10.1080\/21688370.2017.1356901"}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-018-0002-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s10020-018-0002-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-018-0002-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T20:42:53Z","timestamp":1660596173000},"score":1,"resource":{"primary":{"URL":"https:\/\/molmed.biomedcentral.com\/articles\/10.1186\/s10020-018-0002-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,15]]},"references-count":115,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["2"],"URL":"https:\/\/doi.org\/10.1186\/s10020-018-0002-0","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.732909494.793555348","asserted-by":"object"}]},"ISSN":["1076-1551","1528-3658"],"issn-type":[{"value":"1076-1551","type":"print"},{"value":"1528-3658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,15]]},"assertion":[{"value":"10 January 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participation"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare they have no competing interests as defined by\n                      Molecular Medicine\n                      , or other interests that might be perceived to influence the results and discussion reported in this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"4"}}