Exploring the Impact of Prophylactic Antibiotics During Cesarean Delivery on Neonatal Microbiota: A Comprehensive Review Article

Öz

The use of prophylactic antibiotics during cesarean sections (CS) significantly impacts neonatal health by influencing the early colonization of the gut microbiota. Administered before surgical incision, these antibiotics cross the placenta, exposing the fetus to microbial disruptions at a critical stage of immune system development. This study examines the effects of perinatal antibiotic exposure on neonatal gut microbiota composition and its long-term health implications. Findings indicate that antibiotics disrupt microbial diversity, reduce beneficial bacteria like Bifidobacterium, and promote colonization by opportunistic pathogens. Such alterations have been linked to increased risks of obesity, inflammatory bowel disease, and metabolic disorders later in life. Maternal antibiotic use also affects vertical microbial transmission, altering the maternal vaginal and gut microbiota and exposing newborns to antibiotic residues through breast milk. While prophylactic antibiotics effectively reduce perinatal infections, their widespread use raises concerns about antibiotic resistance and long-term health consequences. Experimental studies show that even a single dose during critical developmental windows can predispose neonates to chronic diseases. This study highlights the need for careful evaluation of antibiotic use during the perinatal period to minimize adverse effects on neonatal microbiota and optimize long-term health outcomes. Identifying modifiable risk factors and refining clinical guidelines are essential steps toward balancing the benefits of infection prevention with the risks of microbiota disruption.

Anahtar Kelimeler

• Prophylactic Antibiotics
• Cesarean Section
• Neonatal Microbiota
• Microbial Diversity

Sezaryen Doğumlarda Kullanılan Profilaktik Antibiyotiklerin Yenidoğan Mikrobiyotası Üzerindeki Uzun Vadeli Etkileri: İnceleme Makalesi

Öz

Sezaryen doğumlarda (CS) kullanılan profilaktik antibiyotikler, yenidoğan sağlığı üzerinde önemli etkiler yaratarak bağırsak mikrobiyotasının erken kolonizasyonunu etkilemektedir. Cerrahi kesiden önce uygulanan bu antibiyotikler plasentayı geçerek fetüsü, bağışıklık sisteminin gelişiminde kritik bir aşamada mikrobiyal bozulmalara maruz bırakmaktadır. Bu çalışma, perinatal dönemde antibiyotik maruziyetinin yenidoğan bağırsak mikrobiyotası üzerindeki etkilerini ve bunun uzun vadeli sağlık sonuçlarını incelemektedir. Bulgular, antibiyotiklerin mikrobiyal çeşitliliği bozduğunu, Bifidobacterium gibi faydalı bakterilerin azalmasına ve fırsatçı patojenlerin kolonizasyonunun artmasına yol açtığını göstermektedir. Bu tür değişimlerin, ilerleyen yaşamda obezite, inflamatuvar bağırsak hastalıkları ve metabolik bozukluklar riskini artırdığı tespit edilmiştir. Anneye uygulanan antibiyotikler ayrıca, maternal vajinal ve bağırsak mikrobiyotasını değiştirerek mikrobiyal dikey geçişi etkilemekte ve anne sütü yoluyla antibiyotik kalıntılarına maruz kalmaya neden olmaktadır. Profilaktik antibiyotikler perinatal enfeksiyonları etkili bir şekilde azalttığı halde, yaygın kullanımları antibiyotik direnci ve uzun vadeli sağlık üzerindeki olumsuz etkilerle ilgili endişelere yol açmaktadır. Deneysel çalışmalar, kritik gelişim dönemlerinde tek bir terapötik dozun bile yenidoğanlarda kronik hastalıklara yatkınlık oluşturabilecek mikrobiyota değişimlerine neden olabileceğini göstermektedir. Bu çalışma, perinatal dönemde antibiyotik kullanımının dikkatle değerlendirilmesi gerektiğini, yenidoğan mikrobiyotasına yönelik olumsuz etkilerin en aza indirilmesi ve uzun vadeli sağlık sonuçlarının optimize edilmesi için modifiye edilebilir risk faktörlerinin belirlenmesinin önemini vurgulamaktadır. Enfeksiyon önlemenin faydaları ile mikrobiyota bozulmalarının risklerini dengelemek amacıyla klinik kılavuzların yeniden gözden geçirilmesi kritik öneme sahiptir.

Anahtar Kelimeler

• Profilaktik Antibiyotikler
• Sezaryen Doğum
• Yenidoğan Mikrobiyotası
• Mikrobiyal Çeşitlilik

Kaynakça

1. Macpherson AJ, de Agüero MG, Ganal-Vonarburg SC. How nutrition and the maternal microbiota shape the neonatal immune system. Nat Rev Immunol. 2017;17(8):508-517. doi: 10.1038/nri.2017.58
2. Martino C, Dilmore AH, Burcham ZM, Metcalf JL, Jeste D, Knight R. Microbiota succession throughout life from the cradle to the grave. Nat Rev Microbiol. 2022;20(12):707-720. doi: 10.1038/s41579-022-00720-9
3. Sato Y, Sakurai K, Tanabe H, Kato T, Nakanishi Y, Ohno H, Mori C. Maternal gut microbiota is associated with newborn anthropometrics in a sex-specific manner. J Dev Orig Health Dis. 2019;10(6):659-666. doi: 10.1017/S2040174419000286
4. Haro C, Garcia-Carpintero S, Alcala-Diaz JF, Gomez-Delgado F, Delgado-Lista J, Perez-Martinez P, Rangel Zuniga OA, Quintana-Navarro GM, Landa BB, Clemente JC, Lopez-Miranda J, Camargo A, Perez-Jimenez F. The gut microbial community in metabolic syndrome patients is modified by diet. J Nutr Biochem. 2016;27:27-31. doi: 10.1016/j.jnutbio.2015.08.012
5. Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Bäckhed HK, Gonzalez A, Werner JJ, Angenent LT, Knight R, Bäckhed F, Isolauri E, Salminen S, Ley RE. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470-80. doi: 10.1016/j.cell.2012.07.008
6. Thorburn AN, McKenzie CI, Shen S, Stanley D, Macia L, Mason LJ, Roberts LK, Wong CH, Shim R, Robert R, Chevalier N, Tan JK, Mariño E, Moore RJ, Wong L, McConville MJ, Tull DL, Wood LG, Murphy VE, Mattes J, Gibson PG, Mackay CR. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat Commun. 2015;6:7320. doi: 10.1038/ncomms8320
7. Sarkar A, Yoo JY, Valeria Ozorio Dutra S, Morgan KH, Groer M. The association between early-life gut microbiota and long-term health and diseases. J Clin Med. 2021;10(3):459. doi: 10.3390/jcm10030459
8. Liang D, Leung RKK, Guan W, Au WW. Involvement of gut microbiome in human health and disease: Brief overview, knowledge gaps and research opportunities. Gut Pathog. 2018;10(1):1-9. doi: 10.1186/s13099-018-0230-4

9. Jiménez E, Marín ML, Martín R, Odriozola JM, Olivares M, Xaus J. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159(3):187-193. doi: 10.1016/j.resmic.2007.12.007
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;6:1-13. doi: 10.1038/srep23129
11. Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol Mol Biol Rev. 2017;81(4):1-67. doi: 10.1128/MMBR.00036-17
12. 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, Wang J. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe. 2015;17(6):852. doi: 10.1016/j.chom.2015.05.012
13. Dierikx TH, Visser DH, Benninga MA, van Kaam AHLC, de Boer NKH, de Vries R, Van Limbergen J, De Meij TGJ. The influence of prenatal and intrapartum antibiotics on intestinal microbiota colonisation in infants: A systematic review. J Infect. 2020;81(2):190-204. doi: 10.1016/j.jinf.2020.04.011
14. Russell SL, Gold MJ, Hartmann M, Willing BP, Thorson L, Wlodarska M, Gill N, Blanchet MR, Mohn WW, McNagny KM, Finlay BB. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 2012;13(5):440-7. doi: 10.1038/embor.2012.32
15. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D, Zárate Rodriguez JG, Rogers AB, Robine N, Loke P, Blaser MJ. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158(4):705-721. doi: 10.1016/j.cell.2014.05.052
16. García-Mantrana I, Selma-Royo M, González S, Parra-Llorca A, Martínez-Costa C, Collado MC. Distinct maternal microbiota clusters are associated with diet during pregnancy: impact on neonatal microbiota and infant growth during the first 18 months of life. Gut Microbes. 2020;11(4):962-978. doi: 10.1080/19490976.2020.1712987
17. Ma J, Li Z, Zhang W, Zhang C, Zhang Y, Mei H, Zhuo N, Wang H, Wang L, Wu D. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants. Sci Rep. 2020;10(1):15792. doi: 10.1038/s41598-020-72851-7
18. Ho NT, Li F, Lee-Sarwar KA, Tun HM, Brown BP, Pannaraj PS, Bender JM, Azad MB, Thompson AL, Weiss ST, Azcarate-Peril MA, Litonjua AA, Kozyrskyj AL, Jaspan HB, Aldrovandi GM, Kuhn L. Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations. Nat Commun. 2018;9(1):4169. doi: 10.1038/s41467-018-06473-x
19. Al Nabhani Z, Dulauroy S, Marques R, Cousu C, Al Bounny S, Déjardin F, Sparwasser T, Bérard M, Cerf-Bensussan N, Eberl G. A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult. Immunity. 2019;50(5):1276-1288.e5. doi: 10.1016/j.immuni.2019.03.020
20. Goodrich JK, Davenport ER, Beaumont M, Jackson MA, Knight R, Ober C, Spector TD, Bell JT, Clark AG, Ley RE. Genetic Determinants of the Gut Microbiome in UK Twins. Cell Host Microbe. 2016;19(5):731-43. doi: 10.1016/j.chom.2016.04.017
21. Sarkar A, Yoo JY, Valeria Ozorio Dutra S, Morgan KH, Groer M. The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases. J Clin Med. 2021;10(3):459. doi: 10.3390/jcm10030459
22. Boudry G, Charton E, Le Huerou-Luron I, Ferret-Bernard S, Le Gall S, Even S. The relationship between breast milk components and the infant gut microbiota. Front Nutr. 2021;8:1-21. doi: 10.3389/fnut.2021.644666
23. Arrieta MC, Stiemsma LT, Amenyogbe N, Brown E, Finlay B. The intestinal microbiome in early life: Health and disease. Front Immunol. 2014;5:427. doi: 10.3389/fimmu.2014.00427
24. Bergström A, Skov TH, Bahl MI, Roager HM, Christensen LB, Ejlerskov KT. Establishment of intestinal microbiota during early life: A longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol. 2014;80(9):2889-900. doi: 10.1128/AEM.00342-14
25. Duranti S, Lugli GA, Mancabelli L, Armanini F, Turroni F, James K. Maternal inheritance of bifidobacterial communities and bifidophages in infants through vertical transmission. Microbiome. 2017;5(1):1-13. doi: 10.1186/s40168-017-0248-5
26. Duranti S, Lugli GA, Milani C, James K, Mancabelli L, Turroni F. Bifidobacterium bifidum and the infant gut microbiota: an intriguing case of microbe-host co-evolution. Environ Microbiol. 2019;21(10):3683-95. doi: 10.1111/1462-2920.14756
27. Turroni F, Milani C, Duranti S, Lugli GA, Bernasconi S, Margolles A. The infant gut microbiome as a microbial organ influencing host well-being. Ital J Pediatr. 2020;46(1):1-13. doi: 10.1186/s13052-020-0773-8
28. Vallès Y, Artacho A, Pascual-García A, Ferrús ML, Gosalbes MJ, Abellán JJ. Microbial succession in the gut: directional trends of taxonomic and functional change in a birth cohort of Spanish infants. PLoS Genet. 2014;10(6):e1004406. doi: 10.1371/journal.pgen.1004406
29. 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, Kuczynski 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(7402):222-7. doi: 10.1038/nature11053
30. Kalbermatter C, Fernandez Trigo N, Christensen S, Ganal-Vonarburg SC. Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn. Front Immunol. 2021;12:683022. doi:10.3389/fimmu.2021.683022
31. Penders J, Stobberingh EE, van den Brandt PA, Thijs C. The role of the intestinal microbiota in the development of atopic disorders. Allergy. 2007;62(11):1223-36. doi: 10.1111/j.1398-9995.2007.01462.x
32. 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(11):e78257. doi: 10.1371/journal.pone.0078257
33. 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(3):e90784. doi: 10.1371/journal.pone.0090784
34. Funkhouser LJ, Bordenstein SR. Mom knows best: the universality of maternal microbial transmission. PLoS Biol. 2013;11(8):e1001631. doi: 10.1371/journal.pbio.1001631
35. Dror DK, Allen LH. Overview of nutrients in human milk. Adv Nutr. 2018;9(suppl_1):278S-294S. doi: 10.1093/advances/nmy022
36. Walker A. Breast milk as the gold standard for protective nutrients. J Pediatr. 2010;156(2 Suppl):S3-7. doi: 10.1016/j.jpeds.2009.11.021
37. Fallani M, Amarri S, Uusijarvi A, Adam R, Khanna S, Aguilera M, Gil A, Vieites JM, Norin E, Young D, Scott JA, Doré J, Edwards CA. 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(Pt 5):1385-1392. doi: 10.1099/mic.0.042143-0
38. Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014;5:427. doi: 10.3389/fimmu.2014.00427
39. Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R, Rodríguez JM. The human milk microbiota: origin and potential roles in health and disease. Pharmacol Res. 2013;69(1):1-10. doi: 10.1016/j.phrs.2012.09.001
40. Andres A, Cleves MA, Bellando JB, Pivik RT, Casey PH, Badger TM. Developmental status of 1-year-old infants fed breast milk, cow's milk formula, or soy formula. Pediatrics. 2012;129(6):1134-40. doi:10.1542/peds.2011-3121
41. Pozo-Rubio T, Capilla A, Mujico JR, De Palma G, Marcos A, Sanz Y, Polanco I, García-Novo MD, Castillejo G, Ribes-Koninckx C, Varea V, Palau F, Ortigosa L, Peña-Quintana L, Nova E. Influence of breastfeeding versus formula feeding on lymphocyte subsets in infants at risk of coeliac disease: the PROFICEL study. Eur J Nutr. 2013;52(2):637-46. doi: 10.1007/s00394-012-0372-4
42. Whelan K, Quigley EM. Probiotics in the management of irritable bowel syndrome and inflammatory bowel disease. Curr Opin Gastroenterol. 2013;29(2):184-9. doi: 10.1097/MOG.0b013e32835d7bba
43. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, Welling GW. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr. 2000;30(1):61-7. doi: 10.1097/00005176-200001000-00019
44. Solís G, De Los Reyes-Gavilan CG, Fernández N, Margolles A, Gueimonde M. Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut. Anaerobe. 2010;16(3):307-10. doi: 10.1016/j.anaerobe.2010.03.001
45. Marques TM, Wall R, Ross RP, Fitzgerald GF, Ryan CA, Stanton C. Programming infant gut microbiota: influence of dietary and environmental factors. Curr Opin Biotechnol. 2010;21(2):149-56. doi: 10.1016/j.copbio.2010.03.020
46. Musilova S, Modrackova N, Doskocil I, Svejstil R, Rada V. Influence of human milk oligosaccharides on adherence of bifidobacteria and clostridia to cell lines. Acta Microbiol Immunol Hung. 2017;64(4):415-422. doi: 10.1556/030.64.2017.049
47. Martín R, Jiménez E, Heilig H, Fernández L, Marín ML, Zoetendal EG, Rodríguez JM. Isolation of bifidobacteria from breast milk and assessment of the bifidobacterial population by PCR-denaturing gradient gel electrophoresis and quantitative real-time PCR. Appl Environ Microbiol. 2009;75(4):965-9. doi: 10.1128/AEM.02063-08
48. Martín R, Heilig GHJ, Zoetendal EG, Smidt H, Rodríguez JM. Diversity of the Lactobacillus group in breast milk and vagina of healthy women and potential role in the colonization of the infant gut. J Appl Microbiol. 2007;103:2638-2644. doi: 10.1111/j.1365-2672.2007.03497.x
49. Scott FI, Horton DB, Mamtani R, Haynes K, Goldberg DS, Lee DY, Lewis JD. Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity. Gastroenterology. 2016;151(1):120-129.e5. doi: 10.1053/j.gastro.2016.03.006
50. Shao X, Ding X, Wang B, Li L, An X, Yao Q, Song R, Zhang JA. Antibiotic Exposure in Early Life Increases Risk of Childhood Obesity: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2017;8:170. doi: 10.3389/fendo.2017.00170
51. Alm B, Erdes L, Möllborg P, Pettersson R, Norvenius SG, Aberg N, Wennergren G. Neonatal antibiotic treatment is a risk factor for early wheezing. Pediatrics. 2008;121(4):697-702. doi: 10.1542/peds.2007-1232