Early life microbial colonization is critical for the development of the immune system, postnatal growth, and long-term health and disease. The dynamic and nascent microbiomes of children are highly individualized and are characterized by low bacterial diversity. Any disruptions in microbial colonization can contribute to shifts in normal microbial colonization that persist past the first 1000 days of life and result in intestinal dysbiosis. Here, we focus on microbiome-host interactions during fetal, newborn, and infant microbiome development. We summarize the roles of bacterial communities in fetal development and adverse health outcomes due to dysbiosis. We also discuss how internal and external factors program the microbiome's metabolic machinery as it evolves into an adult-like microbiome. Finally, we discuss the limits of current studies and future directions. Studies on the early-life microbiome will be critical for a better understanding of childhood health and diseases, as well as restorative methods for the prevention and treatment of diseases in adulthood.
Nicolas A, Kenna KP, Renton AE, et al. Genome-wide analyses identify KIF5A as a novel ALS gene. Neuron 2018;97:1268–1283. DOI: 10.1016/j.neuron.2018.02.027.
Koenig JE, Spor A, Scalfone N, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A 2011;108 Suppl 1:4578–4585. DOI: 10.1073/pnas.1000081107.
Backhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015;17:852. DOI: 10.1016/j.chom.2015.05.012.
Arevalo P, VanInsberghe D, Elsherbini J, et al. A reverse ecology approach based on a biological definition of microbial populations. Cell 2019;178:820–834.e14. DOI: 10.1016/j.cell.2019.06.033.
Bokulich NA, Chung J, Battaglia T, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med 2016;8:343ra82. DOI: 10.1126/scitranslmed.aad7121.
Yassour M, Vatanen T, Siljander H, et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 2016;8:343ra81. DOI: 10.1126/scitranslmed.aad0917.
Osmond C, Barker DJ, Winter PD, et al. Early growth and death from cardiovascular disease in women. BMJ 1993;307:1519–1524. DOI: 10.1136/bmj.307.6918.1519.
Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986;1:1077–1081. DOI: 10.1016/s0140-6736(86)91340-1.
Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature 2012;486:222–227. DOI: 10.1038/nature11053.
Vemuri R, Shankar EM, Chieppa M, et al. Beyond just bacteria: functional biomes in the gut ecosystem including virome, mycobiome, archaeome and helminths. Microorganisms 2020;8:483. DOI: 10.3390/microorganisms8040483.
Koren O, Goodrich JK, Cullender TC, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 2012;150:470–480. DOI: 10.1016/j.cell.2012.07.008.
DiGiulio DB, Callahan BJ, McMurdie PJ, et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci U S A 2015;112:11060–11065. DOI: 10.1073/pnas.1502875112.
Kozyrskyj AL, Kalu R, Koleva PT, et al. Fetal programming of overweight through the microbiome: boys are disproportionately affected. J Dev Orig Health Dis 2016;7:25–34. DOI: 10.1017/S2040174415001269.
Kumari M, Kozyrskyj AL. Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation. Obes Rev 2017;18:18–31. DOI: 10.1111/obr.12484.
Tun HM, Bridgman SL, Chari R, et al. Roles of birth mode and infant gut microbiota in intergenerational transmission of overweight and obesity from mother to offspring. JAMA Pediatr 2018;172:368–377. DOI: 10.1001/jamapediatrics.2017.5535.
Ponzo V, Fedele D, Goitre I, et al. Diet-gut microbiota interactions and gestational diabetes mellitus (GDM). Nutrients 2019;11:33. DOI: 10.3390/nu11020330.
Kuang YS, Lu JH, Li SH, et al. Connections between the human gut microbiome and gestational diabetes mellitus. Gigascience 2017;6:1–12. DOI: 10.1093/gigascience/gix058.
Romano-Keeler J, Weitkamp JH. Maternal influences on fetal microbial colonization and immune development. Pediatr Res 2015;77:189–195. DOI: 10.1038/pr.2014.163.
Perez-Munoz ME, Arrieta MC, Ramer-Tait AE, et al. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 2017;5:48. DOI: 10.1186/s40168-017-0268-4.
Aagaard KM. Author response to comment on “the placenta harbors a unique microbiome”. Sci Transl Med 2014;6:254lr3. DOI: 10.1126/scitranslmed.3010007.
Collado MC, Rautava S, Aakko J, et al. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep 2016;6:23129. DOI: 10.1038/srep23129.
Romano-Keeler J, Moore DJ, Wang C, et al. Early life establishment of site-specific microbial communities in the gut. Gut Microbes 2014;5:192–201. DOI: 10.4161/gmic.28442.
Dominguez-Bello MG, Costello EK, 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. DOI: 10.1073/pnas.1002601107.
Betran AP, Ye J, Moller AB, et al. Trends and projections of caesarean section rates: global and regional estimates. BMJ Glob Health 2021;6:e005671. DOI: 10.1136/bmjgh-2021-005671.
Betran AP, Ye J, Moller AB, et al. The increasing trend in caesarean section rates: global, regional and national estimates: 1990-2014. PLoS One 2016;11:e0148343. DOI: 10.1371/journal.pone.0148343.
Black M, Bhattacharya S, Philip S, et al. Planned repeat cesarean section at term and adverse childhood health outcomes: a record-linkage study. PLoS Med 2016;13:e1001973. DOI: 10.1371/journal.pmed.1001973.
Polidano C, Zhu A, Bornstein JC. The relation between cesarean birth and child cognitive development. Sci Rep 2017;7:11483. DOI: 10.1038/s41598-017-10831-y.
Biasucci G, Rubini M, Riboni S, et al. Mode of delivery affects the bacterial community in the newborn gut. Early Hum Dev 2010;86 Suppl 1:13–15. DOI: 10.1016/j.earlhumdev.2010.01.004.
Shao Y, Forster SC, Tsaliki E, et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature 2019;574:117–121. DOI: 10.1038/s41586-019-1560-1.
Jakobsson HE, Abrahamsson TR, Jenmalm MC, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut 2014;63:559–566. DOI: 10.1136/gutjnl-2012-303249.
Mitchell CM, Mazzoni C, Hogstrom L, et al. Delivery mode affects stability of early infant gut microbiota. Cell Rep Med 2020;1:100156. DOI: 10.1016/j.xcrm.2020.100156.
Korpela K, Helve O, Kolho KL, et al. Maternal fecal microbiota transplantation in cesarean-born infants rapidly restores normal gut microbial development: a proof-of-concept study. Cell 2020;183:324–334.e5. DOI: 10.1016/j.cell.2020.08.047.
Grier A, Qiu X, Bandyopadhyay S, et al. Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth. Microbiome 2017;5:158. DOI: 10.1186/s40168-017-0377-0.
Lu L, Claud EC. Intrauterine inflammation, epigenetics, and microbiome influences on preterm infant health. Curr Pathobiol Rep 2018;6:15–21. DOI: 10.1007/s40139-018-0159-9.
Rouge C, Goldenberg O, Ferraris L, et al. Investigation of the intestinal microbiota in preterm infants using different methods. Anaerobe 2010;16:362–370. DOI: 10.1016/j.anaerobe.2010.06.002.
Magne F, Abely M, Boyer F, et al. Low species diversity and high interindividual variability in faeces of preterm infants as revealed by sequences of 16S rRNA genes and PCR-temporal temperature gradient gel electrophoresis profiles. FEMS Microbiol Ecol 2006;57:128–138. DOI: 10.1111/j.1574-6941.2006.00097.x.
Wang Y, Hoenig JD, Malin KJ, et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J 2009;3(8):944–954. DOI: 10.1038/ismej.2009.37.
Nissila E, Korpela K, Lokki AI, et al. C4B gene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease. Clin Exp Immunol 2017;190:394–405. DOI: 10.1111/cei.13040.
Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 2012;129:e827–e841. DOI: 10.1542/peds.2011-3552.
Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: a review on its composition and bioactivity. Early Hum Dev 2015;91(11):629–635. DOI: 10.1016/j.earlhumdev.2015.08.013.
Plunkett CH, Nagler CR. The influence of the microbiome on allergic sensitization to food. J Immunol 2017;198:581–589. DOI: 10.4049/jimmunol.1601266.
Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 2018;562:589–594. DOI: 10.1038/s41586-018-0620-2.
Moles L, Gomez M, Heilig H, et al. Bacterial diversity in meconium of preterm neonates and evolution of their fecal microbiota during the first month of life. PLoS One 2013;8:e66986. DOI: 10.1371/journal.pone.0066986.
Yap PSX, Chong CW, Ahmad Kamar A, et al. Neonatal intensive care unit (NICU) exposures exert a sustained influence on the progression of gut microbiota and metabolome in the first year of life. Sci Rep 2021;11:1353. DOI: 10.1038/s41598-020-80278-1.
Brooks B, Firek BA, Miller CS, et al. 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.
Laursen MF, Zachariassen G, Bahl MI, et al. Having older siblings is associated with gut microbiota development during early childhood. BMC Microbiol 2015;15:154. DOI: 10.1186/s12866-015-0477-6.
Snijders BE, Damoiseaux JG, Penders J, et al. Cytokines and soluble CD14 in breast milk in relation with atopic manifestations in mother and infant (KOALA Study). Clin Exp Allergy 2006;36:1609–1615. DOI: 10.1111/j.1365-2222.2006.02613.x.
Adlerberth I, Strachan DP, Matricardi PM, et al. Gut microbiota and development of atopic eczema in 3 European birth cohorts. J Allergy Clin Immunol 2007;120:343–350. DOI: 10.1016/j.jaci.2007.05.018.
Rodriguez JM, Murphy K, Stanton C, 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.
De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 2010;107:14691–14696. DOI: 10.1073/pnas.1005963107.
Ayeni FA, Biagi E, Rampelli S, et al. Infant and adult gut microbiome and metabolome in rural bassa and urban settlers from Nigeria. Cell Rep 2018;23:3056–3067. DOI: 10.1016/j.celrep.2018.05.018.
Wang M, Ahrne S, Antonsson M, et al. T-RFLP combined with principal component analysis and 16S rRNA gene sequencing: an effective strategy for comparison of fecal microbiota in infants of different ages. J Microbiol Methods 2004;59:53–69. DOI: 10.1016/j.mimet.2004.06.002.
Thompson AL, Monteagudo-Mera A, Cadenas MB, et al. Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front Cell Infect Microbiol 2015;5:3. DOI: 10.3389/fcimb.2015.00003.
Bergstrom A, Skov TH, Bahl MI, et al. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol 2014;80: 2889–2900. DOI: 10.1128/AEM.00342-14.
Fallani M, Amarri S, Uusijarvi A, et al. Determinants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centres. Microbiology (Reading) 2011;157:1385–1392. DOI: 10.1099/mic.0.042143-0.
Laursen MF, Andersen LB, Michaelsen KF, et al. Infant gut microbiota development is driven by transition to family foods independent of maternal obesity. mSphere 2016;1:e00069-15. DOI: 10.1128/mSphere.00069-15.
Oki K, Akiyama T, Matsuda K, et al. Long-term colonization exceeding six years from early infancy of Bifidobacterium longum subsp. longum in human gut. BMC Microbiol 2018;18:209. DOI: 10.1186/s12866-018-1358-6.
O'Neill I, Schofield Z, Hall LJ. Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases. Emerg Top Life Sci 2017;1:333–349. DOI: 10.1042/ETLS20170058.
Schwartz BS, Pollak J, Bailey-Davis L, et al. Antibiotic use and childhood body mass index trajectory. Int J Obes (Lond) 2016;40:615–621. DOI: 10.1038/ijo.2015.218.
Horton DB, Scott FI, Haynes K, et al. Antibiotic exposure and juvenile idiopathic arthritis: a case-control study. Pediatrics 2015;136:e333–e343. DOI: 10.1542/peds.2015-0036.
Azad MB, Konya T, Maughan H, et al. Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity. Allergy Asthma Clin Immunol 2013;9:15. DOI: 10.1186/1710-1492-9-15.
Romano-Keeler J, Zhang J, Sun J. COVID-19 and the neonatal microbiome: will the pandemic cost infants their microbes? Gut Microbes 2021;13:1–7. DOI: 10.1080/19490976.2021.1912562.
Eisenhofer R, Minich JJ, Marotz C, et al. Contamination in low microbial biomass microbiome studies: issues and recommendations. Trends Microbiol 2019;27:105–117. DOI: 10.1016/j.tim.2018.11.003.
McCann A, Ryan FJ, Stockdale SR, et al. Viromes of one year old infants reveal the impact of birth mode on microbiome diversity. Peer J 2018;6:e4694. DOI: 10.7717/peerj.4694.
Maqsood R, Rodgers R, Rodriguez C, et al. Discordant transmission of bacteria and viruses from mothers to babies at birth. Microbiome 2019;7:156. DOI: 10.1186/s40168-019-0766-7.
Fouhy F, Ross RP, Fitzgerald GF, et al. Composition of the early intestinal microbiota: knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps. Gut Microbes 2012;3:203–220. DOI: 10.4161/gmic.20169.
Qin Y, Wade PA. Crosstalk between the microbiome and epigenome: messages from bugs. J Biochem 2018;163:105–112. DOI: 10.1093/jb/mvx080.
Amatullah H, Jeffrey KL. Epigenome-metabolome-microbiome axis in health and IBD. Curr Opin Microbiol 2020;56:97–108. DOI: 10.1016/j.mib.2020.08.005.
Schleif W, Hamblin F, Everett AD, et al. Tiny bodies, big needs: prospective biobanking of neonatal clinical remnant samples. Biopreserv Biobank 2021;19:106–110. DOI: 10.1089/bio.2020.0113.
Integrative HMPRNC. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 2014;16:276–289. DOI: 10.1016/j.chom.2014.08.014.