Development of the preterm infant gut microbiome: a research priority

Maureen W Groer, Angel A Luciano, Larry J Dishaw, Terri L Ashmeade, Elizabeth Miller, Jack A Gilbert, Maureen W Groer, Angel A Luciano, Larry J Dishaw, Terri L Ashmeade, Elizabeth Miller, Jack A Gilbert

Abstract

The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. The paper concludes with speculation about how the VLBW infants' gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.

Keywords: Gut microbiota; Health; Preterm infants; VLBW.

References

    1. Dishaw LJ, Cannon JP, Litman GW, Parker W. Immune-directed support of rich microbial communities in the gut has ancient roots. Dev Comp Immunol. 2014;47:36–51. doi: 10.1016/j.dci.2014.06.011.
    1. Friedrich MJ. Genomes of microbes inhabiting the body offer clues to human health and disease. JAMA. 2013;309:1447–1449. doi: 10.1001/jama.2013.2824.
    1. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kyczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–227.
    1. Pfeiffer JK, Sonnenburg JL. The intestinal microbiota and viral susceptibility. Front Microbiol. 2011;2:92.
    1. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449:804–810. doi: 10.1038/nature06244.
    1. Neu J. Perinatal and neonatal manipulation of the intestinal microbiome: a note of caution. Nutr Rev. 2007;65:282–285. doi: 10.1111/j.1753-4887.2007.tb00305.x.
    1. Jeurink PV, Van Bergenhenegouwen J, Jimenez E, Knippels LM, Fernandez L, Garssen J, Knol J, Rodriguez JM, Martin R. Human milk: a source of more life than we imagine. Benef Microb. 2013;4:17–30. doi: 10.3920/BM2012.0040.
    1. Jimenez E, Marin ML, Martin R, Odriozola JM, Olivares M, Xaus J, Fernandez L, Rodriguez JM. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159:187–193. doi: 10.1016/j.resmic.2007.12.007.
    1. Ardissone AN, De la Cruz DM, Davis-Richardson AG, Rechcigl KT, Li N, Drew JC, Murgas-Torrazza R, Sharma R, Hudak ML, Triplett EW, Neu J. Meconium microbiome analysis identifies bacteria correlated with premature birth. PLoS One. 2014;9:e90784. doi: 10.1371/journal.pone.0090784.
    1. Martinez-Lopez DG, Funderburg NT, Cerissi A, Rifaie R, Aviles-Medina L, Llorens-Bonilla BJ, Sleasman J, Luciano AA. Lipopolysaccharide and soluble CD14 in cord blood plasma are associated with prematurity and chorioamnionitis. Pediatr Res. 2014;75:67–74. doi: 10.1038/pr.2013.182.
    1. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R. 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. doi: 10.1073/pnas.1002601107.
    1. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Chari RS, Sears MR, Becker AB, Scott JA, Kozyrskyj AL. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ. 2013;185:385–394. doi: 10.1503/cmaj.121189.
    1. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177. doi: 10.1371/journal.pbio.0050177.
    1. Guaraldi F, Salvatori G. Effect of breast and formula feeding on gut microbiota shaping in newborns. Front Cell Infect Microbiol. 2012;2:94.
    1. Putignani L, Del Chierico F, Petrucca A, Vernocchi P, Dallapiccola B. The human gut microbiota: a dynamic interplay with the host from birth to senescence settled during childhood. Pediatr Res. 2014;76:2–10. doi: 10.1038/pr.2014.49.
    1. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13:260–270.
    1. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336:1268–1273. doi: 10.1126/science.1223490.
    1. Cebra JJ. Influences of microbiota on intestinal immune system development. Am J Clin Nutr. 1999;69:1046S–1051S.
    1. Bode L. Human milk oligosaccharides: prebiotics and beyond. Nutr Rev. 2009;67(Suppl 2):S183–S191.
    1. Weng M, Walker WA. The role of gut microbiota in programming the immune phenotype. J Dev Orig Health Dis. 2013;4:203–214. doi: 10.1017/S2040174412000712.
    1. 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;17:478–482. doi: 10.1016/j.anaerobe.2011.03.009.
    1. Underwood MA, Kalanetra KM, Bokulich NA, Mirmiran M, Barile D, Tancredi DJ, German JB, Lebrilla CB, Mills DA. Prebiotic oligosaccharides in premature infants. J Pediatr Gastroenterol Nutr. 2014;58:352–360. doi: 10.1097/MPG.0000000000000211.
    1. Martin R, Langa S, Reviriego C, Jiminez E, Marin ML, Xaus J, Fernandez L, Rodriguez JM. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr. 2003;143:754–758. doi: 10.1016/j.jpeds.2003.09.028.
    1. De Leoz ML, Gaerlan SC, Strum JS, Dimapasoc LM, Mirmiran M, Tancredi DJ, Smilowitz JT, Kalanetra KM, Mills DA, German JB, Lebrilla CB, Underwood MA. Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm. J Proteome Res. 2012;11:4662–4672. doi: 10.1021/pr3004979.
    1. Jakaitis BM, Denning PW. Commensal and probiotic bacteria may prevent NEC by maturing intestinal host defenses. Pathophysiology. 2014;21:47–54. doi: 10.1016/j.pathophys.2013.11.012.
    1. Kaplan JL, Shi HN, Walker WA. The role of microbes in developmental immunologic programming. Pediatr Res. 2011;69:465–472. doi: 10.1203/PDR.0b013e318217638a.
    1. Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr. 2009;98:229–238. doi: 10.1111/j.1651-2227.2008.01060.x.
    1. Johansson ME, Sjovall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol. 2013;10:352–361. doi: 10.1038/nrgastro.2013.35.
    1. Maynard CL, Elson CO, Hatton RD, Weaver CT. Reciprocal interactions of the intestinal microbiota and immune system. Nature. 2012;489:231–241. doi: 10.1038/nature11551.
    1. Nieuwdorp M, Gilijamse PW, Pai N, Kaplan LM. Role of the microbiome in energy regulation and metabolism. Gastroenterology. 2014;146:1525–1533. doi: 10.1053/j.gastro.2014.02.008.
    1. Mischke M, Plosch T. More than just a gut instinct—the potential interplay between a baby's nutrition, its gut microbiome, and the epigenome. Am J Physiol Regul Integr Comp Physiol. 2013;304:R1065–R1069. doi: 10.1152/ajpregu.00551.2012.
    1. Poroyko V, Morowitz M, Bell T, Ulanov A, Wang M, Donovan S, Bao N, Gu S, Hong L, Alverdy JC, Bergelson J, Liu DC. Diet creates metabolic niches in the “immature gut” that shape microbial communities. Nutr Hosp. 2011;26:1283–1295.
    1. Brooks B, Firek BA, Miller CS, Sharon I, Thomas BC, Baker R, Morowitz MJ, Banfield JF. Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants. Microbiome. 2014;2:1. doi: 10.1186/2049-2618-2-1.
    1. Moore AM, Patel S, Forsberg KJ, Wang B, Bentley G, Razia Y, Qin X, Tarr PI, Dantas G. Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes. PLoS One. 2013;8:e78822. doi: 10.1371/journal.pone.0078822.
    1. Brown CT, Sharon I, Thomas BC, Castelle CJ, Morowitz MJ, Banfield JF. Genome resolved analysis of a premature infant gut microbial community reveals a Varibaculum cambriense genome and a shift towards fermentation-based metabolism during the third week of life. Microbiome. 2013;1:30. doi: 10.1186/2049-2618-1-30.
    1. La Rosa PS, Warner BB, Zhou Y, Weinstock GM, Sodergren E, Hall-Moore CM, Stevens HJ, Bennett WE Jr, Shaikh N, Linneman LA, Hoffman JA, Hamvas A, Deych E, Shands BA, Shannon WD, Tarr PI. Patterned progression of bacterial populations in the premature infant gut. Proc Natl Acad Sci U S A. 2014;111:12522–12527. doi: 10.1073/pnas.1409497111.
    1. Carl MA, Ndao IM, Springman AC, Manning SD, Johnson JR, Johnston BD, Burnham CA, Weinstock ES, Weinstock GM, Wylie TN, Mitreva M, Abubucker S, Stevens HJ, Hall-Moore C, Julian S, Shaikh N, Warner BB, Tarr PI. Sepsis from the gut: the enteric habitat of bacteria that cause late-onset neonatal bloodstream infections. Clin Infect Dis. 2014;58:1211–1218. doi: 10.1093/cid/ciu084.
    1. Berrington JE, Stewart CJ, Cummings SP, Embleton ND. The neonatal bowel microbiome in health and infection. Curr Opin Infect Dis. 2014;27:236–243. doi: 10.1097/QCO.0000000000000061.
    1. Barrett E, Kerr C, Murphy K, O'Sullivan O, Ryan CA, Dempsey EM, Murphy BP, O'Toole PW, Cotter PD, Fitzgerald GF, Ross RP, Stanton C. The individual-specific and diverse nature of the preterm infant microbiota. Arch Dis Child Fetal Neonatal Ed. 2013;98:F334–F340. doi: 10.1136/archdischild-2012-303035.
    1. Jacquot A, Neveu D, Aujoulat F, Mercier G, Marchandin H, Jumas-Bilak E, Picaud JC. Dynamics and clinical evolution of bacterial gut microflora in extremely premature patients. J Pediatr. 2011;158:390–396. doi: 10.1016/j.jpeds.2010.09.007.
    1. Hunter CJ, De Plaen IG. Inflammatory signaling in NEC: role of NF-kappaB, cytokines and other inflammatory mediators. Pathophysiology. 2014;21:55–65. doi: 10.1016/j.pathophys.2013.11.010.
    1. Hackam DJ, Good M, Sodhi CP. Mechanisms of gut barrier failure in the pathogenesis of necrotizing enterocolitis: toll-like receptors throw the switch. Semin Pediatr Surg. 2013;22:76–82. doi: 10.1053/j.sempedsurg.2013.01.003.
    1. Meier PP, Bode L. Health, nutrition, and cost outcomes of human milk feedings for very low birthweight infants. Adv Nutr. 2013;4:670–671. doi: 10.3945/an.113.004457.
    1. Rogier EW, Frantz AL, Bruno ME, Wedlund L, Cohen DA, Stromberg AJ, Kaetzel CS. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. Proc Natl Acad Sci U S A. 2014;111:3074–3079. doi: 10.1073/pnas.1315792111.
    1. Corthesy B. Multi-faceted functions of secretory IgA at mucosal surfaces. Front Immunol. 2013;4:185.
    1. Eggesbo M, Moen B, Peddada S, Baird D, Rugtveit J, Midtvedt T, Bushel PR, Sekelja M, Rudi K. Development of gut microbiota in infants not exposed to medical interventions. APMIS. 2011;119:17–35. doi: 10.1111/j.1600-0463.2010.02688.x.
    1. Hack M, Weissman B, Borawski-Clark E. Catch-up growth during childhood among very low-birth-weight children. Arch Pediatr Adolesc Med. 1996;150:1122–1129. doi: 10.1001/archpedi.1996.02170360012002.
    1. Barker DJ, Osmond C, Forsen TJ, Kajantie E, Eriksson JG. Trajectories of growth among children who have coronary events as adults. N Engl J Med. 2005;353:1802–1809. doi: 10.1056/NEJMoa044160.
    1. Belfort MB, Gillman MW, Buka SL, Casey PH, McCormick MC. Preterm infant linear growth and adiposity gain: trade-offs for later weight status and intelligence quotient. J Pediatr. 2013;163:1564–1569. doi: 10.1016/j.jpeds.2013.06.032. e1562.
    1. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Int J Epidemiol. 2013;42:1215–1222. doi: 10.1093/ije/dyt133.
    1. Murphy R, Stewart AW, Braithwaite I, Beasley R, Hancox RJ, Mitchell EA. the IPTSG. Antibiotic treatment during infancy and increased body mass index in boys: an international cross-sectional study. Int J Obes (Lond) 2013;38:1115–1119.
    1. Bervoets L, Van Hoorenbeeck K, Kortleven I, Van Noten C, Hens N, Vael C, Goossens H, Desager KN, Vankerckhoven V. Differences in gut microbiota composition between obese and lean children: a cross-sectional study. Gut Pathog. 2013;5:10. doi: 10.1186/1757-4749-5-10.
    1. Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, De Vos WM, Hoekstra JB, Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–916. doi: 10.1053/j.gastro.2012.06.031. e917.
    1. Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010;92:1023–1030. doi: 10.3945/ajcn.2010.29877.
    1. Thompson AL. Developmental origins of obesity: early feeding environments, infant growth, and the intestinal microbiome. Am J Hum Biol. 2012;24:350–360. doi: 10.1002/ajhb.22254.
    1. Serenius F, Kallen K, Blennow M, Ewald U, Fellman V, Holmstrom G, Lindberg E, Lundqvist P, Marsal K, Norman M, Olhager E, Stigson L, Stjernqvist K, Vollmer B, Stromberg B. Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden. JAMA. 2013;309:1810–1820. doi: 10.1001/jama.2013.3786.
    1. Bora S, Pritchard VE, Chen Z, Inder TE, Woodward LJ. Neonatal cerebral morphometry and later risk of persistent inattention/hyperactivity in children born very preterm. J Child Psychol Psychiatry. 2014;55:828–838. doi: 10.1111/jcpp.12200.
    1. Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR. EPICure Study Group. Neurologic and developmental disability after extremely preterm birth. N Engl J Med. 2000;343:378–384. doi: 10.1056/NEJM200008103430601.
    1. Douglas-Escobar M, Elliott E, Neu J. Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr. 2013;167:374–379. doi: 10.1001/jamapediatrics.2013.497.
    1. Cryan JF, O'Mahony SM. The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil. 2011;23:187–192. doi: 10.1111/j.1365-2982.2010.01664.x.
    1. Hornig M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol. 2013;25:488–795. doi: 10.1097/BOR.0b013e32836208de.
    1. Kuzniewicz MW, Wi S, Qian Y, Walsh EM, Armstrong MA, Croen LA. Prevalence and neonatal factors associated with autism spectrum disorders in preterm infants. J Pediatr. 2014;164:20–25. doi: 10.1016/j.jpeds.2013.09.021.
    1. Goyal DK, Miyan JA. Neuro-immune abnormalities in autism and their relationship with the environment: a variable insult model for autism. Front Endocrinol (Lausanne) 2014;5:29.
    1. Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011;11:22. doi: 10.1186/1471-230X-11-22.
    1. Gilbert Jack A, Krajmalnik-Brown R, Porazinska Dorota L, Weiss Sophie J, Knight R. Toward effective probiotics for autism and other neurodevelopmental disorders. Cell. 2013;155:1446–1448. doi: 10.1016/j.cell.2013.11.035.
    1. Centanni M, Turroni S, Consolandi C, Rampelli S, Peano C, Severgnini M, Biagi E, Caredda G, De Bellis G, Brigidi P, Candela M. The enterocyte-associated intestinal microbiota of breast-fed infants and adults responds differently to a TNF-α-mediated pro-inflammatory stimulus. PLoS One. 2013;8:e81762. doi: 10.1371/journal.pone.0081762.
    1. Eggesbo M, Botten G, Stigum H, Nafstad P, Magnus P. Is delivery by cesarean section a risk factor for food allergy? J Allergy Clin Immunol. 2003;112:420–426. doi: 10.1067/mai.2003.1610.
    1. Murk W, Risnes KR, Bracken MB. Prenatal or early-life exposure to antibiotics and risk of childhood asthma: a systematic review. Pediatrics. 2011;127:1125–1138. doi: 10.1542/peds.2010-2092.
    1. Risnes KR, Belanger K, Murk W, Bracken MB. Antibiotic exposure by 6 months and asthma and allergy at 6 years: findings in a cohort of 1,401 US children. Am J Epidemiol. 2011;173:310–318. doi: 10.1093/aje/kwq400.
    1. Mejia-Leon ME, Petrosino JF, Ajami NJ, Dominguez-Bello MG, De la Barca AM. Fecal microbiota imbalance in Mexican children with type 1 diabetes. Sci Rep. 2014;4:3814.
    1. Hviid A, Svanstrom H, Frisch M. Antibiotic use and inflammatory bowel diseases in childhood. Gut. 2011;60:49–54. doi: 10.1136/gut.2010.219683.

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