Acquisition of microbiota according to the type of birth: an integrative review

this integrative review addresses the role of the type of delivery on newborns’ microbial colonization. A search was conducted in the Medical Literature Analysis and Retrieval System Online/PubMed and Virtual Health Library databases using the descriptors provided by Medical Subject Headings (MeSH) and Health Science Descriptors (DeCS).

Results:

infants born vaginally presented a greater concentration of Bacteroides, Bifidobacteria, and Lactobacillus in the first days of life and more significant microbial variability in the following weeks. The microbiome of infants born via C-section is similar to the maternal skin and the hospital setting and less diverse, mainly composed of Staphylococcus, Streptococcus, and Clostridium.

Conclusion:

the maternal vaginal microbiota provides newborns with a greater variety of colonizing microorganisms responsible for boosting and preparing the immune system. Vaginal birth is the ideal birth route, and C-sections should only be performed when there are medical indications.

Descriptors:
Microbiota; Obstetric Delivery; Cesarean Section; Parturition; Immune System; Newborn Infant

Authors	Year	Study design/Level of evidence	Main Results
Liu, et al.⁽²¹21 Liu CJ, Liang X, Niu ZY, Jin Q, Zeng XQ, Wang WX, et al. Is the delivery mode a critical factor for the microbial communities in the meconium? EBioMedicinE. 2019 Nov; 49:354-63. doi: 10.1016/j.ebiom.2019.10.045 https://doi.org/10.1016/j.ebiom.2019.10.... ⁾	2019	Well-designed controlled trial without randomization/III	Only samples of the amniotic fluid showed significant differences (p<0.001) according to the type of birth. While meconium, placenta, and fetal membrane samples showed no significant differences between newborns born vaginally or via C-section. Vaginal delivery: Lactobacillus and Gardnerella; C-section: Thermus and Tepidiphilus.
Reyman, et al.⁽²²22 Reyman M, van Houten MA, van Baarle D, Bosch AATM, Man WH, Chu MLJN, et al. Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life. Nat Commun. 2019; Nov 1;10(1):4997. doi: 10.1038/s41467-019-13014-7 https://doi.org/10.1038/s41467-019-13014... ⁾	2019	Cohort/IV	Up to two months of life, the microbial community of children born vaginally was more stable than that of children born via C-section. Abundant Bifidobacteria is associated with the type of delivery, age, and whether the child is breastfed. Breastfeeding, however, does not make up for the lack of Bifidobacteria among children born via C-section. Vaginal delivery: Bifidobacteria and Escherichia; C-section: Klebsiella and Enterococcus.
Li, et al.⁽²³23 Li H, Wang J, Wu L, Luo J, Liang X, Xiao B, Zhu Y. The impacts of delivery mode on infant's oral microflora. Sci Rep. 2018;Aug 9;8(1):11938. doi: 10.1038/s41598-018-30397-7 https://doi.org/10.1038/s41598-018-30397... ⁾	2018	Well-designed controlled trial without randomization/III	The vaginal delivery group has significantly more Bifidobacteria and Akkermansiaceae, showing the beneficial aspect of natural birth. Two common pathogenic bacteria, Providencia and Gardnerella, were also found in some of the infants in this group, which may be explained by the presence of mothers with vaginal infections that had not been manifested.
Shi, et al.⁽²⁴24 Shi YC, Guo H, Chen J, Sun G, Ren RR, Guo MZ, et al. Initial meconium microbiome in Chinese neonates delivered naturally or by cesarean section. Sci Rep. 2018; Feb 19;8(1):3255. doi: 10.1038/s41598-018-21657-7 https://doi.org/10.1038/s41598-018-21657... ⁾	2018	Cohort/IV	The microbiome of children born vaginally is a little more diverse than that of children born via C-section. Vaginal delivery: Actinobacteria, Gammaproteobacteria, and Betaproteobacteria; C-section: Deinococcus, Alphaproteobacteria, and Bacilli.
Wampach, et al.⁽²⁵25 Wampach L, Heintz-Buschart A, Fritz JV, Ramiro-Garcia J, Habier J, Herold M, et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential. Nat Commun. 2018 Nov 30;9(1):5091. doi: 10.1038/s41467-018-07631-x https://doi.org/10.1038/s41467-018-07631... ⁾	2018	Cohort/IV	Type of delivery was considered the dominant driver of the colonization of the neonatal gut microbiome. Vaginal delivery influences the transference of functional characteristics involved in microbial pathways, such as the biosynthesis of lipopolysaccharides that are important in developing a newborn's immune system.
Brazier, et al.⁽²⁶26 Brazier L, Elguero E, Koumavor CK, Renaud N, Prugnolle F, Thomas F, et al. Evolution in fecal bacterial/viral composition in infants of two central African countries (Gabon and Republic of the Congo) during their first month of life. PLoS One. 2017 Oct 02;12(10):1-19. doi: 10.1371/journal.pone.0185569 https://doi.org/10.1371/journal.pone.018... ⁾	2017	Well-designed controlled trial without randomization/III	The type of delivery influenced the fecal microbial composition. Vaginal delivery: Bacteroides and Collinsella; C-section: Klebsiella and Sarcina.
Chu, et al.⁽²⁷27 Chu DM, Ma J, Prince AL, Antony KM, Seferovic MD, Aagaard KM. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nature Med. 2017 Jan 23;23:314-26. doi: 10.1038/nm.4272 https://doi.org/10.1038/nm.4272... ⁾	2017	Cohort/IV	The neonatal microbial community structure at the time of delivery did not show significant differences according to the body's site. Vaginal delivery: Lactobacillus; C-section: Propionibacterium and Streptococcus. The microbiota of newborns born vaginally tended to be similar to their mothers' vagina, while infants born via elective C-sections were mainly populated by the microbiota found on their mothers' skin.
Hill, et al.⁽²⁸28 Hill CJ, Lynch DB, Murphy K, Ulaszewska M, Jeffery IB, O'Shea CA, et al. Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort. Microbiome. 2017 Jan 17;5(21):1-18. doi: 10.1186/s40168-016-0213-y https://doi.org/10.1186/s40168-016-0213-... ⁾	2017	Cohort/IV	The structure of an infant's gut microbiota is affected by the type of delivery. Vaginal birth: Bifidobacteria, Bacteroides; C-section: Clostridium. A large diversity of individual population structures was found within each group, showing the heterogeneous gut microbiota composition of developing infants.
Bokulich, et al.⁽²⁹29 Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Science Translational Medicine. 2016 Jun 15;8(343):343-82. doi: 10.1126/scitranslmed.aad7121 https://doi.org/10.1126/scitranslmed.aad... ⁾	2016	Well-designed controlled trial without randomization/III	The children born via C-section showed a significantly greater phylogenetic diversity (p<0.05). However, these significantly decreased during the first month after birth while these children subsequently presented a lower diversity and less richness up to 2 years of age.
Bosch, et al.⁽³⁰30 Bosch AATM, Levin E, Van Houten MA, Hasrat R, Kalkman G, Biesbroek G, et al. Development of Upper Respiratory Tract Microbiota in Infancy is Affected by Mode of Delivery. EBioMedicine. 2016 Jul;9:336-45. doi: 10.1016/j.ebiom.2016.05.031 https://doi.org/10.1016/j.ebiom.2016.05.... ⁾	2016	Cohort/IV	Children born vaginally tend to change profiles dominated by Moraxella and Corynebacterium/Dolosigranulum in an earlier stage than children born via C-section, who remain longer in a profile dominated by S. aureus.
Brumbaugh, et al.⁽³¹31 Brumbaugh DE, Arruda J, Robbins K, Ir D, Santorico AS, Robertson CE, et al. Mode of Delivery Determines Neonatal Pharyngeal Bacterial Composition and Early Intestinal Colonization. JPGN. 2016 Sep;63(3):320-8. doi: 10.1097/MPG.0000000000001124 https://doi.org/10.1097/MPG.000000000000... ⁾	2016	Well-designed controlled trial without randomization/III	Significant differences were found at the phylum level and bacterial abundance at a gender level, according to the type of delivery for all the infants' samples. Vaginal delivery: Oropharynx: Firmicutes (Lactobacillus). Fecal samples: Bacteroidetes; C-section: Oropharynx: Actinobacteria (Propionibacterium) and Proteobacteria. Fecal samples: Proteobacteria. Disturbances in colonization and succession within the human gut in early life may influence the risk of long-term illnesses.
Dominguez-Bello, et al.⁽¹²12 Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature Med. 2016 Feb 01;(22):250-3. doi: 10.1038/nm.4039 https://doi.org/10.1038/nm.4039... ⁾	2016	Well-designed controlled trial without randomization/III	Regardless of the body site, the microbiome of infants born vaginally or via C-section were more similar to their mothers' vaginal microbiome, when exposed to vaginal fluid, than that of infants born via C-section but not exposed.
Kristensen; Herinksen⁽³²32 Kristensen K, Henriksen L. Cesarean section and disease associated with immune function. J Allergy Clin Immunol. 2016 Feb;137(2):587-90. doi: 10.1016/j.jaci.2015.07.040 https://doi.org/10.1016/j.jaci.2015.07.0... ⁾	2016	Cohort/IV	C-section was associated with infection and inflammation of the mucosa. The effect of elective C-sections was more significant for asthma than emergency C-sections. Estimates of respiratory tract disease did not change after adjusting for neonatal respiratory morbidity.
Martin, et al.⁽³³33 Martin R, Makino H, Yavuz AC, Ben-Amor K, Roelofs M, Ishikawa E, et al. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota. PLoS One. 2016 Jun 30;11(6):1-30. doi: 10.1371/journal.pone.0158498 https://doi.org/10.1371/journal.pone.015... ⁾	2016	Cross-sectional/VI	The type of delivery was one of the factors that strongly impacted the initial composition of newborns' microbiota. The infants born vaginally had significantly higher bacterial counts in the meconium than those born by C-section. Infants born via C-section had late colonization of various groups of bacterial species. Vaginal birth: Bifidobacterium, Bacteroides fragilis, B. ovatus, B. vulgatus, B. uniformis, B. caccae, and B. longum subsp. Longum; C-section: Enterococcus and C. perfringens.
Shilts, et al.⁽³⁴34 Shilts MH, Rosas-Salazar C, Tovchigrechko A, Larkin EK, Torralba M, Akopov A, et al. Minimally Invasive Sampling Method Identifies Differences in Taxonomic Richness of Nasal Microbiomes in Young Infants Associated with Mode of Delivery. Microbial Ecol. 2016 Jan;71(1):233-42. doi: 10.1007/s00248-015-0663-y https://doi.org/10.1007/s00248-015-0663-... ⁾	2016	Cohort/IV	The taxonomic profile of the nasal microbiome of infants born vaginally was closer to the nasal microbiome previously found in adults, compared to infants born via C-section. This finding supports the hypothesis that the nasal microbiome of infants born vaginally may represent an environment successfully colonized by stable commensal microbiota. Vaginal delivery: Actinobacteria (Corynebacterium); C-section: Firmicutes (Staphylococcus).
Stokholm, et al.⁽³⁵35 Stokholm J, Thorsen J, Chawes BL, Schjørring S, Krogfelt KA, Bønnelykke K, et al. Cesarean section changes neonatal gut colonization. J Allergy Clin Immunol. 2016 Sep;138(3):881-9. doi: 10.1016/j.jaci.2016.01.028 https://doi.org/10.1016/j.jaci.2016.01.0... ⁾	2016	Cohort/IV	Type of birth was associated with different gut bacterial colonization patterns in early childhood, which normalizes during the first year of life. Elective and emergency C-sections were associated with distinctly different colonization patterns. Vaginal birth: E. coli; C-section: Citrobacter freundii, Enterobacter cloacae, Enterococcus faecalis, Klebsiella oxytoca, Klebsiella pneumoniae, and Staphylococcus aureus.\
Bäckhed, et al.⁽³⁶36 Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe. 2015 May 13;17(5):690-703. doi: 10.1016/j.chom.2015.04.004 https://doi.org/10.1016/j.chom.2015.04.0... ⁾	2015	Cohort/IV	The route of birth strongly affected the microbiome species in neonates. Vaginal birth: Bacteroides, Bifidobacterium, Parabacteroides, Escherichia/Shigella; C-section: Enterobacter sp., Haemophilus sp., Staphylococcus sp., Streptococcus australis, and Veillonella sp.
Dogra, et al.⁽³⁷37 Dogra S, Sakwinska O, Soh SE, Ngom-Bru C, Brück WM, Berger B, et al. Dynamics of infant gut microbiota are influenced by delivery mode and gestational duration and are associated with subsequent adiposity. mBio. 2015 Feb 03;6(1):1-9. doi: 10.1128/mBio.02419-14 https://doi.org/10.1128/mBio.02419-14... ⁾	2015	Cohort/IV	The bacteria colonizing newborns' bodies promote a long-lasting effect in the immune system or on the gut barrier function, driven by the type of delivery. Vaginal birth: Bifidobacterium and Collinsella. C-section: Klebsiella, Enterobacteriaceae, and Streptococcus. A lower or later colonization by Bifidobacteria was found among infants born via C-section; Bifidobacteria are considered to be ideal in a newborn's organism.
Dong, et al.⁽³⁸38 Dong L, Jialin Y, Luquan L, Qing A, Jinxing F, Chao S, et al. Bacterial Community Structure Associated With Elective Cesarean Section Versus Vaginal Delivery in Chinese Newborns. JPGN. 2015 Feb;60(2):240-6. doi: 10.1097/MPG.0000000000000606 https://doi.org/10.1097/MPG.000000000000... ⁾	2015	Cross-sectional/VI	The route of the birth delivery had a more significant impact on the gut microbiota structure than on its diversity during the first 4 days of life. Vaginal birth: DAY 2: E coli and Bacteroides sp. DAY 4: Bifidobacterium sp and Bacteroides sp; C-section: DAY 2: Staphylococcus sp, Clostridium sp, and Enterobacter sp. DAY 4: Clostridium sp and Streptococcus sp.
Hesla, et al.⁽³⁹39 Hesla HM, Stenius F, Jaderlund L, Nelson R, Engstrand L, Alm J, et al. Impact of lifestyle on the gut microbiota of healthy infants and their mothers - the ALADDIN birth cohort. FEMS Microbiol Ecol. 2014 Dec 01;90(1):791-801. doi: 10.1111/1574-6941.12434 https://doi.org/10.1111/1574-6941.12434... ⁾	2014	Cohort/IV	Vaginal birth: Bacteroides. C-section: Enterobacteriaceae, Clostridium, Haemophilus, Veillonella.
Jakobsson, et al.⁽⁴⁰40 Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg C, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2014;63(4):559-66. doi: 10.1136/gutjnl-2012-303249 https://doi.org/10.1136/gutjnl-2012-3032... ⁾	2014	Well-designed controlled trial without randomization/III	A lower microbial diversity was found among infants born via C-section and lower circulating levels of the Th1-type chemokines, CXCL10 and CXCL11.
Makino, et al.⁽⁴¹41 Makino H, Kushiro A, Ishikawa E, Kubota H, Gawad A, Sakai T, et al. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant's microbiota. PLoS One. 2013 Nov 14;8(11):1-10. doi: 10.1371/journal.pone.0078331 https://doi.org/10.1371/journal.pone.007... ⁾	2013	Well-designed controlled trial without randomization/III	The number of Bifidobacteria was significantly lower among infants born through C-section than among infants born vaginally up to 7 days of age. Bifidobacteria gut colonization is considered to begin more rapidly among infants born vaginally than among infants born through C-sections.
Pandey, et al.⁽⁴²42 Pandey PK, Verma P, Kumar H, Bavdekar A, Patole MS, Shouche YS. Comparative analysis of fecal microflora of healthy full-term Indian infants born with different methods of delivery (vaginal vs cesarean): Acinetobacter sp. prevalence in vaginally born infants. Bioscience J. 2012 Dec;31(1):989-98. doi: 10.1007/s12038-012-9268-5 https://doi.org/10.1007/s12038-012-9268-... ⁾	2012	Well-designed controlled trial without randomization/III	The initial colonization and acquisition of gut microbiota may strongly influence the status of cellular and humoral elements of the immune system of the gut mucosa during a newborn's life. Vaginal delivery: Staphylococcus haemolyticus; Acinetobacter sp., Bifidobacterium sp. C-section: Roseomonas pecuniae, Paracoccus sp., Enterococcus sp., Streptococcus vestibularis, Chryseomicrobium imtechense, and Staphylococcus sp., Clostridium difficile, Citrobacter sp. and Escherichia coli.
Biasucci, et al.⁽⁴³43 Biasucci G, Rubini M, Riboni S, Morelli L, Bessi E, Retetangos C. Mode of delivery affects the bacterial community in the newborn gut. Early Hum Dev. 2010 Jun;86(1):13-5. doi: 10.1016/j.earlhumdev.2010.01.004 https://doi.org/10.1016/j.earlhumdev.201... ⁾	2010	Well-designed controlled trial without randomization/III	The study reports Bifidobacterium's presence in 13 of the 23 (56.5%) samples from infants born vaginally, but not in the samples obtained from infants born via C-section.
Dominguez-Bello, et al.⁽⁴⁴44 Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. PNAS. 2010 Jun 29;107(26):11971-5. doi: 10.1073/pnas.1002601107 https://doi.org/10.1073/pnas.1002601107... ⁾	2010	Randomized Clinical Trial/I	The newborns harbored bacterial communities that were essentially undifferentiated on the skin, nasal, nasopharynx, and gut habitats, regardless of the type of birth delivery. These results show that human microbiota is homogeneously distributed throughout the body in the early stage of community development.

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[1] Corresponding author: Gabriela Diniz Pinto Coelho E-mail: gaabi.dpc@hotmail.com