A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: Implications for research on the pioneer infant microbiome

Microbiome

Volumn 5, Issue 1, 2017, Pages

  Perez Muñoz, Maria Elisa ^a   Arrieta, Marie Claire ^b   Ramer Tait, Amanda E ^c   Walter, Jens ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

^c UNIVERSITY OF NEBRASKA LINCOLN   (United States)

Author keywords

Axenic animals; Contamination; In utero colonization; Microbiome; Placenta; Sterile womb

Indexed keywords

AMNION FLUID; BACTERIAL VIABILITY; CESAREAN SECTION; FETUS DEVELOPMENT; GERMFREE ANIMAL; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL MEMORY; INFANT; INTESTINE FLORA; MECONIUM; MICROBIAL COLONIZATION; MICROBIAL COMMUNITY; MICROBIAL CONTAMINATION; NONHUMAN; PLACENTA; PREGNANCY; PRIORITY JOURNAL; REVIEW; UTERUS; VAGINAL DELIVERY; ANIMAL; FEMALE; FETUS; MICROBIOLOGY; MICROFLORA; NEWBORN;

ANIMALS; FEMALE; FETUS; GASTROINTESTINAL MICROBIOME; HUMANS; INFANT; INFANT, NEWBORN; MICROBIOTA; PREGNANCY; UTERUS;

EID: 85022198188     PISSN: None     EISSN: 20492618     Source Type: Journal    
DOI: 10.1186/s40168-017-0268-4     Document Type: Review

References (151)

1. Chow J, Lee SM, Shen Y, Khosravi A, Mazmanian SK. Host-bacterial symbiosis in health and disease. Adv Immunol. 2010;107:243-74.
2. Arrieta M-C, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Britton HM, Lefebvre DL, Subbarao P, Mandhane P, Becker A, McNagny KM, Sears MR, Kollmann T, Mohn WW, Turvey SE, Brett Finlay B. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med. 2015;7:307ra152.
3. Koleva PT, Kim J-S, Scott JA, Kozyrskyj AL. Microbial programming of health and disease starts during fetal life. Birth Defects Res C Embryo Today. 2015; 105:265-77.
4. Funkhouser LJ, Bordenstein SR. Mom knows best: the universality of maternal microbial transmission. PLoS Biol. 2013;11:e1001631.
5. Bright M, Bulgheresi S. A complex journey: transmission of microbial symbionts. Nat Rev Microbiol. 2010;8:218-30.
6. Kustner O. Beitrag zur Lehre von der puerperalen Infection der Neugeborenen. Arch Gynakol. 1877;11:256-63.
7. Escherich T. The intestinal bacteria of the neonate and breast-fed infant. Rev Infect Dis. 1885;11:352-6.
8. Jiménez E, Marín ML, Martín R, Odriozola JM, Olivares M, Xaus J, Fernández L, Rodríguez JM. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159:187-93.
9. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6:237ra65.
10. Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016;6:23129.
11. Blaser MJ, Dominguez-Bello MG. The human microbiome before birth. Cell Host Microbe. 2016;20:558-60.
12. Burrage S. Bacteria in the supposedly sterile meconium. J Bacteriol. 1927;13:47.
13. Hau IC, O'Toole E, Hall IP. Bacterial flora of first specimens of meconium passed by fifty newborn infants. Am J Dis Child. 1934;47:1279-85.
14. Hansen R, Scott KP, Khan S, Martin JC, Berry SH, Stevenson M, Okpapi A, Munro MJ, Hold GL. First-pass meconium samples from healthy term vaginally-delivered neonates: an analysis of the microbiota. PLoS One. 2015; 10:e0133320.
15. Harris JW, Brown JH. The bacterial content of the uterus at cesaren section. Am J Obstet Gynecol. 1927;13:133-43.
16. Stroup PE. Amniotic fluid infection and the intact fetal membrane. Obstet Gynecol. 1962;19:736-9.
17. Harwick HJ, Iuppa JB, Fekety FR. Microorganisms and amniotic fluid. Obstet Gynecol. 1969;33:256-9.
18. Prevedourakis C, Papadimitriou G, Ioannidou A. Isolation of pathogenic bacteria in the amniotic fluid during pregnancy and labor. Am J Obstet Gynecol. 1970;106:400-2.
19. Prevedourakis CN, Strigou-Charalabis E, Kaskarelis DB. Bacterial invasion of amniotic cavity during pregnancy and labor. Obstet Gynecol. 1971;37:459-61.
20. Lewis JF, Johnson P, Miller P. Evaluation of amniotic fluid for aerobic and anaerobic bacteria. Am J Clin Pathol. 1976;65:58-63.
21. Evaldson GR, Malmborg AS, Nord CE. Premature rupture of the membranes and ascending infection. Br J Obstet Gynaecol. 1982;89:793-801.
22. Ovalle A, Martínez MA, Kakarieka E, Gómez R, Torres J, Fuentes A, Ruiz M, Angel R. Placental histopathology in premature rupture of membranes. Its relationship with microbiological findings, maternal, and neonatal outcome. Rev Médica Chile. 1998;126:930-42.
23. Greig PC. The diagnosis of intrauterine infection in women with preterm premature rupture of the membranes (PPROM). Clin Obstet Gynecol. 1998; 41:849-63.
24. Gravett MG, Hummel D, Eschenbach DA, Holmes KK. Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol. 1986;67:229-37.
25. Martius J, Eschenbach DA. The role of bacterial vaginosis as a cause of amniotic fluid infection, chorioamnionitis and prematurity-a review. Arch Gynecol Obstet. 1990;247:1-13.
26. DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch F, Kim CJ, Erez O, Edwin S, Relman DA. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One. 2008;3:e3056.
27. DiGiulio DB, Gervasi M, Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic JP, Seok KS, Gómez R, Mittal P, Gotsch F, Chaiworapongsa T, Oyarzún E, Kim CJ, Relman DA. Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. J Perinat Med. 2010;38:503-13.
28. DiGiulio DB, Gervasi MT, Romero R, Vaisbuch E, Mazaki-Tovi S, Kusanovic JP, Seok KS, Gómez R, Mittal P, Gotsch F, Chaiworapongsa T, Oyarzún E, Kim CJ, Relman DA. Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-age fetuses. J Perinat Med. 2010;38:495-502.
29. DiGiulio DB, Romero R, Kusanovic JP, Gómez R, Kim CJ, Seok KS, Gotsch F, Mazaki-Tovi S, Vaisbuch E, Sanders K, Bik EM, Chaiworapongsa T, Oyarzún E, Relman DA. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol. 2010;64:38-57.
30. Wang X, Buhimschi CS, Temoin S, Bhandari V, Han YW, Buhimschi IA. Comparative microbial analysis of paired amniotic fluid and cord blood from pregnancies complicated by preterm birth and early-onset neonatal sepsis. PLoS One. 2013;8:e56131.
31. DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med. 2012;17:2-11.
32. Burton G, Watson A. The structure of the human placenta: implications for initiating and defending against virus infections. Rev Med Virol. 1997;7:219-28.
33. Robbins JR, Bakardjiev AI. Pathogens and the placental fortress. Curr Opin Microbiol. 2012;15:36-43.
34. Bartizal FJ, Pacheco JC, Malkasian GD, Washington JA. Microbial flora found in the products of conception in spontaneous abortions. Obstet Gynecol. 1974;43:109-12.
35. Aquino TI, Zhang J, Kraus FT, Knefel R, Taff T. Subchorionic fibrin cultures for bacteriologic study of the placenta. Am J Clin Pathol. 1984;81:482-6.
36. Maszkiewicz W, Rzeszutko-Adamiczka D, Kalinski R. Results of histological examinations of afterbirth and other parameters of threatening infection in newborns at high risk of infection. Mater Med Pol. 1991;23:111-6.
37. Steel JH, Malatos S, Kennea N, Edwards AD, Miles L, Duggan P, Reynolds PR, Feldman RG, Sullivan MHF. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res. 2005;57:404-11.
38. Stout MJ, Conlon B, Landeau M, Lee I, Bower C, Zhao Q, Roehl KA, Nelson DM, Macones GA, Mysorekar IU. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations. Am J Obstet Gynecol. 2013;208:226.e1-7.
39. Wassenaar TM, Panigrahi P. Is a foetus developing in a sterile environment? Lett Appl Microbiol. 2014;59:572-9.
40. Mitchell CM, Haick A, Nkwopara E, Garcia R, Rendi M, Agnew K, Fredricks DN, Eschenbach D. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. Am J Obstet Gynecol. 2015;212:611.e1-9.
41. Verstraelen H, Vilchez-Vargas R, Desimpel F, Jauregui R, Vankeirsbilck N, Weyers S, Verhelst R, De Sutter P, Pieper DH, Van De Wiele T. Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene. PeerJ. 2016;4:e1602.
42. Larsen B, Hwang J. Mycoplasma, ureaplasma, and adverse pregnancy outcomes: a fresh look. Infect Dis Obstet Gynecol. 2010;2010:1-7.
43. Capoccia R, Greub G, Baud D. Ureaplasma urealyticum, Mycoplasma hominis and adverse pregnancy outcomes. Curr Opin Infect Dis. 2013;26:231-40.
44. Pararas MV, Skevaki CL, Kafetzis DA. Preterm birth due to maternal infection: causative pathogens and modes of prevention. Eur J Clin Microbiol Infect Dis. 2006;25:562-9.
45. Cassell GH, Davis RO, Waites KB, Brown MB, Marriott PA, Stagno S, Davis JK. Isolation of Mycoplasma hominis and Ureaplasma urealyticum from amniotic fluid at 16-20 weeks of gestation: potential effect on outcome of pregnancy. Sex Transm Dis. 1983;10(4 Suppl):294-302.
46. Horowitz S, Mazor M, Romero R, Horowitz J, Glezerman M. Infection of the amniotic cavity with Ureaplasma urealyticum in the midtrimester of pregnancy. J Reprod Med. 1995;40:375-9.
47. Berg TG, Philpot KL, Welsh MS, Sanger WG, Smith CV. Ureaplasma/Mycoplasmainfected amniotic fluid: pregnancy outcome in treated and nontreated patients. J Perinatol. 1999;19:275-7.
48. Nguyen DP, Gerber S, Hohlfeld P, Sandrine G, Witkin SS. Mycoplasma hominis in mid-trimester amniotic fluid: relation to pregnancy outcome. J Perinat Med. 2004;32:323.
49. Antony KM, Ma J, Mitchell KB, Racusin DA, Versalovic J, Aagaard K. The preterm placental microbiome varies in association with excess maternal gestational weight gain. Am J Obstet Gynecol. 2015;212:653.e1-16.
50. Doyle RM, Alber DG, Jones HE, Harris K, Fitzgerald F, Peebles D, Klein N. Term and preterm labour are associated with distinct microbial community structures in placental membranes which are independent of mode of delivery. Placenta. 2014;35:1099-101.
51. Rautava S, ColladoMC, Salminen S, Isolauri E. Probioticsmodulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebocontrolled trial. Neonatology. 2012;102:178-84.
52. Maltepe E, Bakardjiev AI, Fisher SJ. The placenta: transcriptional, epigenetic, and physiological integration during development. J Clin Invest. 2010;120:1016-25.
53. Robbins JR, Skrzypczynska KM, Zeldovich VB, Kapidzic M, Bakardjiev AI. Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes. PLoS Pathog. 2010;6:e1000732.
54. Doran KS, Banerjee A, Disson O, Lecuit M. Concepts and mechanisms: crossing host barriers. Cold Spring Harb Perspect Med. 2013;3:7.
55. Zeldovich VB, Clausen CH, Bradford E, Fletcher DA, Maltepe E, Robbins JR, Bakardjiev AI. Placental syncytium forms a biophysical barrier against pathogen invasion. PLoS Pathog. 2013;9:e1003821.
56. Tarrade A, Lai Kuen R, Malassiné A, Tricottet V, Blain P, Vidaud M, Evain-Brion D. Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta. Lab Invest. 2001;81:1199-211.
57. Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol. 2010;63:425-33.
58. Lecuit M. Understanding how Listeria monocytogenes targets and crosses host barriers. Clin Microbiol Infect. 2005;11:430-6.
59. Yagnik B, Padh H, Desai P. Construction of a new shuttle vector for DNA delivery into mammalian cells using non-invasive Lactococcus lactis. Microbes Infect. 2016;18:237-44.
60. Klaffenbach D, Rascher W, Röllinghoff M, Dötsch J, Meissner U, Schnare M. Regulation and signal transduction of toll-like receptors in human chorioncarcinoma cell lines. Am J Reprod Immunol. 2005;53:77-84.
61. Patni S, Bryant AH, Wynen LP, Seager AL, Morgan G, Thornton CA. Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta. Placenta. 2015;36:1031-8.
62. Abrahams VM, Bole-Aldo P, Kim YM, Straszewski-Chavez SL, Chaiworapongsa T, Romero R, Mor G. Divergent trophoblast responses to bacterial products mediated by TLRs. J Immunol. 2004;173:4286-96.
63. Yarbrough VL, Winkle S, Herbst-Kralovetz MM. Antimicrobial peptides in the female reproductive tract: a critical component of the mucosal immune barrier with physiological and clinical implications. Hum Reprod Update. 2015;21:353-77.
64. Pacora P, Maymon E, Gervasi MT, Gomez R, Edwin SS, Yoon BH, Romero R. Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes. Am J Obstet Gynecol. 2000;183:904-10.
65. Espinoza J, Chaiworapongsa T, Romero R, Edwin S, Rathnasabapathy C, Gomez R, Bujold E, Camacho N, Kim YM, Hassan S, Blackwell S, Whitty J, Berman S, Redman M, Yoon BH, Sorokin Y. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes. J Matern Fetal Neonatal Med. 2003;13:2-21.
66. Kai-Larsen Y, Gudmundsson GH, Agerberth B. A review of the innate immune defence of the human foetus and newborn, with the emphasis on antimicrobial peptides. Acta Paediatr. 2014;103:1000-8.
67. Ben-Hur H, Gurevich P, Berman V, Tchanyshev R, Gurevich E, Zusman I. The secretory immune system as part of the placental barrier in the second trimester of pregnancy in humans. In Vivo. 2001;15:429-35.
68. Gurevich P, Elhayany A, Ben-Hur H, Moldavsky M, Szvalb S, Zandbank J, Shperling I, Zusman I. An immunohistochemical study of the secretory immune system in human fetal membranes and decidua of the first trimester of pregnancy. Am J Reprod Immunol. 2003;50:13-9.
69. Lin CT. Immunoelectron microscopy localization of immunoglobulin G in human placenta. J Histochem Cytochem. 1980;28:339-46.
70. Johnson PM, Natvig JB, Ystehede UA, Faulk WP. Immunological studies of human placentae: the distribution and character of immunoglobulins in chorionic villi. Clin Exp Immunol. 1977;30:145-53.
71. Schelonka RL, Infante AJ. Neonatal immunology. Semin Perinatol. 1998;22:2-14.
72. Velilla PA, Rugeles MT, Chougnet CA. Defective antigen-presenting cell function in human neonates. Clin Immunol. 2006;121:251-9.
73. Patni S, Wynen LP, Seager AL, Morgan G, White JO, Thornton CA. Expression and activity of Toll-like receptors 1-9 in the human term placenta and changes associated with labor at term. Biol Reprod. 2009;80:243-8.
74. Pérez A, Bellón JM, Gurbindo MD, Muñoz-Fernández Má. Impairment of stimulation ability of very-preterm neonatal monocytes in response to lipopolysaccharide. Hum Immunol. 2010;71:151-7.
75. van Elburg RM, Fetter WPF, Bunkers CM, Heymans HSA. Intestinal permeability in relation to birth weight and gestational and postnatal age. Arch Dis Child Fetal Neonatal Ed. 2003;88:F52-5.
76. Kliman HJ. Comment on "The placenta harbors a unique microbiome". Sci Transl Med. 2014;6:254le4.
77. Ispirli H, Demirbas F, Dertli E. Characterization of functional properties of Enterococcus faecium strains isolated from human gut. Can J Microbiol. 2015;61:861-70.
78. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54(Pt 5):1469-76.
79. Tsuzukibashi O, Uchibori S, Shinozaki-Kuwahara N, Kobayashi T, Takada K, Hirasawa M. A selective medium for the isolation of Corynebacterium species in oral cavities. J Microbiol Methods. 2014;104:67-71.
80. Fernandez-Feo M, Wei G, Blumenkranz G, Dewhirst FE, Schuppan D, Oppenheim FG, Helmerhorst EJ. The cultivable human oral gluten-degrading microbiome and its potential implications in coeliac disease and gluten sensitivity. Clin Microbiol Infect. 2013;19:E386-94.
81. Haraszthy VI, Zambon JJ, Sreenivasan PK, Zambon MM, Gerber D, Rego R, Parker C. Identification of oral bacterial species associated with halitosis.J Am Dent Assoc. 2007;138:1113-20.
82. Prohic A, Simic D, Sadikovic TJ, Krupalija-Fazlic M. Distribution of Malassezia species on healthy human skin in Bosnia and Herzegovina: correlation with body part, age and gender. Iran J Microbiol. 2014;6:253-62.
83. Parolin C, Marangoni A, Laghi L, Foschi C, ñahui Palomino RA, Calonghi N, Cevenini R, Vitali B. Isolation of vaginal Lactobacilli and characterization of anti-candida activity. PLoS One. 2015;10:e0131220.
84. Satokari R, Grönroos T, Laitinen K, Salminen S, Isolauri E. Bifidobacterium and Lactobacillus DNA in the human placenta. Lett Appl Microbiol. 2009;48:8-12.
85. Mühl H, Kochem A-J, Disqué C, Sakka SG. Activity and DNA contamination of commercial polymerase chain reaction reagents for the universal 16S rDNA real-time polymerase chain reaction detection of bacterial pathogens in blood. Diagn Microbiol Infect Dis. 2010;66:41-9.
86. Grahn N, Olofsson M, Ellnebo-Svedlund K, Monstein HJ, Jonasson J. Identification of mixed bacterial DNA contamination in broad-range PCR amplification of 16S rDNA V1 and V3 variable regions by pyrosequencing of cloned amplicons. FEMS Microbiol Lett. 2003;219:87-91.
87. Tanner MA, Goebel BM, Dojka MA, Pace NR. Specific ribosomal DNA sequences from diverse environmental settings correlate with experimental contaminants. Appl Environ Microbiol. 1998;64:3110-3.
88. Evans GE, Murdoch DR, Anderson TP, Potter HC, George PM, Chambers ST. Contamination of Qiagen DNA extraction kits with Legionella DNA. J Clin Microbiol. 2003;41:3452-3.
89. van der Zee A, Peeters M, de Jong C, Verbakel H, Crielaard JW, Claas ECJ, Templeton KE. Qiagen DNA extraction kits for sample preparation for legionella PCR are not suitable for diagnostic purposes. J Clin Microbiol. 2002;40:1126.
90. Salter SJ, Cox MJ, Turek EM, Calus ST, Cookson WO, Moffatt MF, Turner P, Parkhill J, Loman NJ, Walker AW. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 2014;12:87.
91. Lauder AP, Roche AM, Sherrill-Mix S, Bailey A, Laughlin AL, Bittinger K, Leite R, Elovitz MA, Parry S, Bushman FD. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome. 2016;4:29.
92. Nagpal R, Tsuji H, Takahashi T, Kawashima K, Nagata S, Nomoto K, Yamashiro Y. Sensitive quantitative analysis of the meconium bacterial microbiota in healthy term infants born vaginally or by cesarean section. Front Microbiol. 2016;7:1997.
93. Jones HE, Harris KA, Azizia M, Bank L, Carpenter B, Hartley JC, Klein N, Peebles D. Differing prevalence and diversity of bacterial species in fetal membranes from very preterm and term labor. PLoS One. 2009;4:e8205.
94. Zoetendal EG, Ben-Amor K, Akkermans ADL, Abee T, de Vos WM. DNA isolation protocols affect the detection limit of PCR approaches of bacteria in samples from the humangastrointestinal tract. Syst Appl Microbiol. 2001; 24:405-10.
95. Milani C, Lugli GA, Turroni F, Mancabelli L, Duranti S, Viappiani A, Mangifesta M, Segata N, van Sinderen D, Ventura M. Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol. FEMS Microbiol Ecol. 2014;90(2):493-503.
96. Sunderarajan K, Kelkar SS. Bacterial flora of meconium and faeces during the first year of life. Indian J Pediatr. 1979;46:92-5.
97. Khoury KA, Floch MH, Hersh T. Small intestinal mucosal cell proliferation and bacterial flora in the conventionalization of the germfree mouse. J Exp Med. 1969;130:659-70.
98. Mshvildadze M, Neu J, Shuster J, Theriaque D, Li N, Mai V. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr. 2010;156:20-5.
99. Hu J, Nomura Y, Bashir A, Fernandez-Hernandez H, Itzkowitz S, Pei Z, Stone J, Loudon H, Peter I. Diversified microbiota of meconium is affected by maternal diabetes status. PLoS One. 2013;8:e78257.
100. Rotimi VO, Duerden BI. The development of the bacterial flora in normal neonates. J Med Microbiol. 1981;14:51-62.
101. 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;107:11971-5.
102. Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG. The infant microbiome development: mom matters. Trends Mol Med. 2014;21:109-17.
103. Voreades N, Kozil A, Weir TL. Diet and the development of the human intestinal microbiome. Front Microbiol. 2014;5:494.
104. Shin H, Pei Z, Martinez KA, Rivera-Vinas JI, Mendez K, Cavallin H, Dominguez-Bello MG. The first microbial environment of infants born by C-section: the operating room microbes. Microbiome. 2015;3:59.
105. Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, Li Y, Xia Y, Xie H, Zhong H, Khan MT, Zhang J, Li J, Xiao L, Al-Aama J, Zhang D, Lee YS, Kotowska D, Colding C, Tremaroli V, Yin Y, Bergman S, Xu X, Madsen L, Kristiansen K, Dahlgren J, Jun W. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17:690-703.
106. Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H, D Lieber A, Wu F, Perez-Perez GI, Chen Y, Schweizer W, Zheng X, Contreras M, Dominguez-Bello MG, Blaser MJ. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016;8:343ra82.
107. 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.
108. 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-800S.
109. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R, Clemente JC. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016;22:250-3.
110. Trexler PC. A rationale for the development of gnotobiotics. Lab Anim. 1978;12:257-62.
111. Heinecke H. The origins of the gnotobiotic technic-Küster/Nuttall/Schottelius/ Thierfelder. Zeitschrift für Versuchstierkd. 1990;33:19-22.
112. Gustafsson B. Germ-free rearing of rats. Acta Anat (Basel). 1946-1947;2:376-91.
113. Reyniers JA, Sacksteder MR. The use of germfree animals and techniques in the search for unknown etiological agents. Ann N Y Acad Sci. 1958;73:344-56.
114. Reyniers JA, Trexler PC, Ervin RF. Rearing germ-free albino rats. Lobund reports. 1946;1:1-84.
115. Landy JJ, Yerasimides TG, Growdon JH, Bausor SC. Germfree guinea pig delivery by hysterectomy. Surg Forum. 1960;11:425-6.
116. Waxler GL, Schmidt DA, Whitehair CK. Technique for rearing gnotobiotic pigs. Am J Vet Res. 1966;27:300-7.
117. Pilgrim HI, Parks RC. Foster nursing of germfree mice. Lab Anim Care. 1968;18:346-51.
118. Stepánková R, Klepalová J, Kruml J. Rearing of germfree rabbits. Folia Microbiol (Praha). 1972;17:505-12.
119. Riou Y, Gouet P, Dubourguier HC, Contrepois M, Dardillat C, Lefaivre J. Techniques for obtaining, fistulization and rearing of axenic or gnotoxenic lambs, kids and calves. Ann Rech vétérinaires Ann Vet Res. 1977;8:13-24.
120. Eichberg JW, Moore GT, Kalter SS, Rodriguez AR, Berchelmann ML. 5Rearing of conventional and gnotobiotic nonhuman primates (Pan troglodytes, Papio cynocephalus, Saguinus nigricollis). J Med Primatol. 1979;8:69-78.
121. Krakowka S, Austin NJ, Long DJ, Helphrey M. Revised surgical procedure for the derivation of gnotobiotic dogs. Am J Vet Res. 1981;42:149-50.
122. Fletcher AM, Hoskins JD, Elkins AD. Germfree technique for the rearing of kittens-a research tool. Cornell Vet. 1991;81:365-78.
123. Heine W. Operating procedures, equipment and housing facilities to maintain small laboratory animals under SPF conditions in large breeding colonies and in experiments. J S Afr Vet Assoc. 1978;49:171-4.
124. Bibiloni R. Rodent models to study the relationships between mammals and their bacterial inhabitants. Gut Microbes. 2012;3:536-43.
125. Hedrich HJ, Hardy P. The laboratory mouse. London: Elsevier; 2012.
126. Barnes RD, Fairweather DV, Holliday J, Keane C, Piesowicz A, Soothill JF, Tuffrey M. A germfree infant. Lancet (London, England). 1969;1:168-71.
127. Wilson R, Mastromarino A. Gnotobiotic human infants. Am J Clin Nutr. 1977; 30:1896-903.
128. Malinak LR, Wilson R, South MA, Montgomery JR, Mumford DM, Flowers CE. Germ-free delivery. The initiation of management of infants with a high probability of congenital immune deficiency states. Am J Obstet Gynecol. 1973;116:201-4.
129. Barnes RD, Fairweather DV, Reynolds EO, Tuffrey M, Holliday J. A technique for the delivery of a germfree child. J Obstet Gynaecol Br Commonw. 1968; 75:689-97.
130. Barnes RD, Bentovim A, Hensman S, Piesowicz AT. Care and observation of a germ-free neonate. Arch Dis Child. 1969;44:211-7.
131. Trávnícek J, Mandel L. Germ-free newborn baby. Nahrung. 1987;31:631-3.
132. Kendall AI. Recent developments in intestinal bacteriology. Am J Med Sci. 1918;156:157-73.
133. Gregory KE, LaPlante RD, Shan G, Kumar DV, Gregas M. Mode of birth influences preterm infant intestinal colonization with bacteroides over the early neonatal period. Adv Neonatal Care. 2015;15:386-93.
134. Dogra S, Sakwinska O, Soh S-E, Ngom-Bru C, Brück WM, Berger B, Brüssow H, Karnani N, Lee YS, Yap F, Chong Y-S, Godfrey KM, Holbrook JD. Rate of establishing the gut microbiota in infancy has consequences for future health. Gut Microbes. 2015;6:321-5.
135. Makino H, Kushiro A, Ishikawa E, Kubota H, Gawad A, Sakai T, Oishi K, Martin R, Ben-Amor K, Knol J, Tanaka R. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant's microbiota. PLoS One. 2013;8:e78331.
136. Huurre A, Kalliomäki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery-effects on gut microbiota and humoral immunity. Neonatology. 2008;93:236-40.
137. Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, Hamelmann E. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol. 2013;132:601-607.e8.
138. 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;38:629-33.
139. Cardwell CR, Stene LC, Joner G, Cinek O, Svensson J, Goldacre MJ, Parslow RC, Pozzilli P, Brigis G, Stoyanov D, Urbonaite B, Šipetic S, Schober E, Ionescu-Tirgoviste C, Devoti G, de Beaufort CE, Buschard K, Patterson CC. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia. 2008;51:726-35.
140. Barros FC, Matijasevich A, Hallal PC, Horta BL, Barros AJ, Menezes AB, Santos IS, Gigante DP, Victora CG. Cesarean section and risk of obesity in childhood, adolescence, and early adulthood: evidence from 3 Brazilian birth cohorts. Am J Clin Nutr. 2012;95:465-70.
141. Charbonneau MR, Blanton LV, DiGiulio DB, Relman DA, Lebrilla CB, Mills DA, Gordon JI. A microbial perspective of human developmental biology. Nature. 2016;535:48-55.
142. Gomez De Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, Steinert A, Heikenwalder M, Hapfelmeier S, Sauer U, McCoy KD, Macpherson AJ. The maternal microbiota drives early postnatal innate immune development. Science (80-). 2016;351:1296-302.
143. Merton RK. The Sociology of Science: Theoretical and empirical investigations. Chicago: University of Chicago Press; 1973.
144. Merton RK, Storer NW, Popper KR. Conjectures and refutations: the growth of scientific knowledge. London: Routledge Class; 2002, 2nd:417.
145. Martínez I, Muller CE, Walter J. Long-term temporal analysis of the human fecal microbiota revealed a stable core of dominant bacterial species. PLoS One. 2013;8:e69621.
146. Segata N, Haake SK, Mannon P, Lemon KP, Waldron L, Gevers D, Huttenhower C, Izard J. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 2012; 13:R42.
147. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207-14.
148. Bergström A, Skov TH, Bahl MI, Roager HM, Christensen LB, Ejlerskov KT, Mølgaard C, Michaelsen KF, Licht TR. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol. 2014;80:2889-900.
149. Gosalbes MJ, Llop S, Vallès Y, Moya A, Ballester F, Francino MP. Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Exp Allergy. 2013;43:198-211.
150. Amarasekara R, Jayasekara RW, Senanayake H, Dissanayake VHW. Microbiome of the placenta in pre-eclampsia supports the role of bacteria in the multifactorial cause of pre-eclampsia. J Obstet Gynaecol Res. 2015;41:662-9.
151. Dong X-D, Li X-R, Luan J-J, Liu X-F, Peng J, Luo Y-Y, Liu C-J. Bacterial communities in neonatal feces are similar to mothers' placentae. Can J Infect Dis Med Microbiol = J Can des Mal Infect la Microbiol médicale/ AMMI Canada. 2015;26:90-4.