Advertisement

The Developing Microbiome of the Preterm Infant

      Abstract

      Purpose

      To determine the importance of the neonatal microbiome in intestinal and overall health.

      Method

      A review of existing literature.

      Findings and Implications

      The microbiome is increasingly understood to have a significant role in health and disease. However, the microbiome of the preterm infant is unique, with simple microbial communities exposed to a consistent diet in a regulated environment, and development from naive to stable under the influence of the neonatal intensive care unit. This early microbiome encounters a still developing host and thus has the potential to program fundamental pathways with implications for neonatal and later outcomes.

      Key words

      To read this article in full you will need to make a payment
      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Cryan J.F.
        • Dinan T.G.
        Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour.
        Nat Rev Neurosci. 2012; 13: 701-712
        • Gritz E.C.
        • Bhandari V.
        The human neonatal gut microbiome: a brief review.
        Front Pediatr. 2015; 3: 17
        • Neu J.
        • Walker W.A.
        Necrotizing enterocolitis.
        N Engl J Med. 2011; 364: 255-264
        • Claud E.C.
        • Walker W.A.
        Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis.
        FASEB J. 2001; 15: 1398-1403
        • Claud E.C.
        Neonatal necrotizing enterocolitis -inflammation and intestinal immaturity.
        Antiinflamm Antiallergy Agents Med Chem. 2009; 8: 248-259
        • Claud E.C.
        • Lu L.
        • Anton P.M.
        • et al.
        Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation.
        Proc Natl Acad Sci U S A. 2004; 101: 7404-7408
        • Yee W.H.
        • Soraisham A.S.
        • Shah V.S.
        • et al.
        Incidence and timing of presentation of necrotizing enterocolitis in preterm infants.
        Pediatrics. 2012; 129: e298-e304
        • Lambert D.K.
        • Christensen R.D.
        • Baer V.L.
        • et al.
        Fulminant necrotizing enterocolitis in a multihospital healthcare system.
        J Perinatol. 2012; 32: 194-198
        • Moss R.L.
        • Dimmitt R.A.
        • Barnhart D.C.
        • et al.
        Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation.
        N Engl J Med. 2006; 354: 2225-2234
        • Hintz S.R.
        • Kendrick D.E.
        • Stoll B.J.
        • et al.
        Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis.
        Pediatrics. 2005; 115: 696-703
        • Patel A.L.
        • Mutlu E.A.
        • Sun Y.
        • et al.
        Longitudinal survey of microbiota in hospitalized preterm very-low-birth-weight infants.
        J Pediatr Gastroenterol Nutr. 2016; 62: 292-303
        • Wang Y.
        • Hoenig J.D.
        • Malin K.J.
        • et al.
        16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis.
        ISME J. 2009; 3: 944-954
        • Claud E.C.
        • Keegan K.P.
        • Brulc J.M.
        • et al.
        Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants.
        Microbiome. 2013; 1: 20
        • Ardissone A.N.
        • de la Cruz D.M.
        • Davis-Richardson A.G.
        • et al.
        Meconium microbiome analysis identifies bacteria correlated with premature birth.
        PLoS One. 2014; 9: e90784
        • Aagaard K.
        • Ma J.
        • Antony K.M.
        • et al.
        The placenta harbors a unique microbiome.
        Sci Transl Med. 2014; 6 (237ra65)
        • Adlerberth I.
        • Wold A.E.
        Establishment of the gut microbiota in Western infants.
        Acta Paediatr. 2009; 98: 229-238
        • Dominguez-Bello M.G.
        • Costello E.K.
        • Contreras M.
        • et al.
        Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.
        Proc Natl Acad Sci U S A. 2010; 107: 11971-11975
        • Gronlund M.M.
        • Lehtonen O.P.
        • Eerola E.
        • Kero P.
        Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery.
        J Pediatr Gastroenterol Nutr. 1999; 28: 19-25
        • Biasucci G.
        • Rubini M.
        • Riboni S.
        • et al.
        Mode of delivery affects the bacterial community in the newborn gut.
        Early Hum Dev. 2010; 86: 13-15
        • Orrhage K.
        • Nord C.E.
        Factors controlling the bacterial colonization of the intestine in breastfed infants.
        Acta Paediatr Suppl. 1999; 88: 47-57
        • Gupta R.W.
        • Tran L.
        • Norori J.
        • et al.
        Histamine-2 receptor blockers alter the fecal microbiota in premature infants.
        J Pediatr Gastroenterol Nutr. 2013; 56: 397-400
        • Berrington J.E.
        • Stewart C.J.
        • Embleton N.D.
        • Cummings S.P.
        Gut microbiota in preterm infants: assessment and relevance to health and disease.
        Arch Dis Child Fetal Neonatal Ed. 2013; 98: F286-F290
        • Lu L.
        • Yu Y.
        • Guo Y.
        • et al.
        Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model.
        PLoS One. 2015; 10: e0124504
        • Ehrenkranz R.A.
        • Dusick A.M.
        • Vohr B.R.
        • et al.
        Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants.
        Pediatrics. 2006; 117: 1253-1261
        • Jarlestedt K.
        • Naylor A.S.
        • Dean J.
        • Hagberg H.
        Mallard C. Decreased survival of newborn neurons in the dorsal hippocampus after neonatal LPS exposure in mice.
        Neuroscience. 2013; 253: 21-28
        • Smith P.L.
        • Hagberg H.
        • Naylor A.S.
        Mallard C. Neonatal peripheral immune challenge activates microglia and inhibits neurogenesis in the developing murine hippocampus.
        Dev Neurosci. 2014; 36: 119-131
        • Vohr B.R.
        • Allen M.
        Extreme prematurity--the continuing dilemma.
        N Engl J Med. 2005; 352: 71-72
        • Keunen K.
        • van Elburg R.M.
        • van Bel F.
        Benders MJ. Impact of nutrition on brain development and its neuroprotective implications following preterm birth.
        Pediatr Res. 2015; 77: 148-155
        • Forsythe P.
        • Kunze W.A.
        Voices from within: gut microbes and the CNS.
        Cell Mol Life Sci. 2013; 70: 55-69
        • Neufeld K.M.
        • Kang N.
        • Bienenstock J.
        • Foster J.A.
        Reduced anxiety-like behavior and central neurochemical change in germ-free mice.
        Neurogastroenterol Motil. 2011; 23: e119
        • Hsiao E.Y.
        • McBride S.W.
        • Hsien S.
        • et al.
        Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.
        Cell. 2013; 155: 1451-1463
        • Doshi-Velez F.
        • Avillach P.
        • Palmer N.
        • et al.
        Prevalence of inflammatory bowel disease among patients with autism spectrum disorders.
        Inflamm Bowel Dis. 2015; 21: 2281-2288
        • Parracho H.M.
        • Bingham M.O.
        • Gibson G.R.
        • McCartney A.L.
        Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.
        J Med Microbiol. 2005; 54: 987-991
        • Macfabe D.F.
        Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders.
        Microb Ecol Health Dis. 2012; : 23
        • Rees C.M.
        • Pierro A.
        • Eaton S.
        Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis.
        Arch Dis Child Fetal Neonatal Ed. 92. 2007: F193-F198
        • Ellison V.J.
        • Mocatta T.J.
        • Winterbourn C.C.
        • et al.
        The relationship of CSF and plasma cytokine levels to cerebral white matter injury in the premature newborn.
        Pediatr Res. 2005; 57: 282-286
        • Sun L.
        Early childhood general anaesthesia exposure and neurocognitive development.
        Br J Anaesth. 2010; 105: i61-i68
        • Ismail I.H.
        • Oppedisano F.
        • Joseph S.J.
        • et al.
        Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants.
        Pediatr Allergy Immunol. 2012; 23: 674-681
        • Kronman M.P.
        • Zaoutis T.E.
        • Haynes K.
        • et al.
        Antibiotic exposure and IBD development among children: a population-based cohort study.
        Pediatrics. 2012; 130: e794-e803
        • Penders J.
        • Thijs C.
        • van den Brandt P.A.
        • et al.
        Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study.
        Gut. 2007; 56: 661-667
        • Saari A.
        • Virta L.J.
        • Sankilampi U.
        • et al.
        Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life.
        Pediatrics. 2015; 135: 617-626
        • Mai V.
        • Young C.M.
        • Ukhanova M.
        • et al.
        Fecal microbiota in premature infants prior to necrotizing enterocolitis.
        PLoS One. 2011; 6: e20647
        • Petrof E.O.
        • Claud E.C.
        • Gloor G.B.
        • Allen-Vercoe E.
        Microbial ecosystems therapeutics: a new paradigm in medicine?.
        Benef Microbes. 2013; 4: 53-65
        • AlFaleh K.
        • Anabrees J.
        Probiotics for prevention of necrotizing enterocolitis in preterm infants.
        Cochrane Database Syst Rev. 2014; 4 (CD005496)
        • Bin-Nun A.
        • Bromiker R.
        • Wilschanski M.
        • et al.
        Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates.
        J Pediatr. 2005; 147: 192-196
        • Lin H.C.
        • Hsu C.H.
        • Chen H.L.
        • et al.
        Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial.
        Pediatrics. 2008; 122: 693-700
        • Lin H.C.
        • Su B.H.
        • Chen A.C.
        • et al.
        Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants.
        Pediatrics. 2005; 115: 1-4
        • Mattar A.F.
        • Drongowski R.A.
        • Coran A.G.
        • Harmon C.M.
        Effect of probiotics on enterocyte bacterial translocation in vitro.
        Pediatr Surg Int. 2001; 17: 265-268
        • Reid G.
        • Howard J.
        • Gan B.S.
        Can bacterial interference prevent infection?.
        Trends Microbiol. 2001; 9: 424-428
        • Duffy L.C.
        Interactions mediating bacterial translocation in the immature intestine.
        J Nutr. 2000; 130: 432S-436SS
        • Link-Amster H.
        • Rochat F.
        • Saudan K.Y.
        • et al.
        Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake.
        FEMS Immunol Med Microbiol. 1994; 10: 55-63
        • Claud E.C.
        First do no harm.
        J Pediatr Pharmacol Ther. 2012; 17: 298-301
        • Meinzen-Derr J.
        • Poindexter B.
        • Wrage L.
        • et al.
        Role of human milk in extremely low birth weight infants׳ risk of necrotizing enterocolitis or death.
        J Perinatol. 2009; 29: 57-62
        • Polin R.A.
        Management of neonates with suspected or proven early-onset bacterial sepsis.
        Pediatrics. 2012; 129: 1006-1015
        • Clark R.H.
        • Bloom B.T.
        • Spitzer A.R.
        • Gerstmann D.R.
        Reported medication use in the neonatal intensive care unit: data from a large national data set.
        Pediatrics. 2006; 117: 1979-1987
        • Gewolb I.H.
        • Schwalbe R.S.
        • Taciak V.L.
        • et al.
        Stool microflora in extremely low birthweight infants.
        Arch Dis Child Fetal Neonatal Ed. 1999; 80: F167-F173
        • Cotten C.M.
        • Taylor S.
        • Stoll B.
        • 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: 58-66