Download PDF
Am J Perinatol 2021; 38(11): 1181-1191
DOI: 10.1055/s-0040-1710559
Original Article

Ongoing Supplementation of Probiotics to Cesarean-Born Neonates during the First Month of Life may Impact the Gut Microbial

Wenqing Yang
1   Department of Neonatal Diagnosis and Treatment Center, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People's Republic of China
2   China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China
3   Chongqing Key Laboratory of Pediatrics, Chongqing Medical University, Chongqing, People's Republic of China
4   Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Liang Tian
4   Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Jiao Luo
4   Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, People's Republic of China
,
Jialin Yu
1   Department of Neonatal Diagnosis and Treatment Center, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People's Republic of China
2   China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China
3   Chongqing Key Laboratory of Pediatrics, Chongqing Medical University, Chongqing, People's Republic of China
› Author Affiliations Funding The research was supported by the National Natural Science Foundation of China (No. 81370744, No. 81571483), Doctoral Degree Funding from Chinese Ministry of Education (No. 20135503110009), State key clinic discipline project (No. 2011-873), and Clinical Research Foundation of Children's Hospital of Chongqing Medical University ((2014)254-lcyj2014-11).
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective The delivery mode is considered to be a significant influencing factor in the early gut microbiota composition, which is associated with the long-term health of the host. In this study, we tried to explore the effects of probiotics on the intestinal microbiota of C-section neonates.

Study Design Twenty-six Chinese neonates were enrolled in this study. The neonates were divided into four groups: VD (natural delivery neonates, n = 3), CD (cesarean-born neonates, n = 9), CDL (cesarean-born neonates supplemented with probiotic at a lower dosage, n = 7), and CDH (cesarean-born neonates supplemented with probiotic at a higher dosage, n = 7). Fecal samples were collected on the 3rd, 7th, and 28th day since birth. The V3–V4 region of the 16S ribosomal ribonucleic acid gene was sequenced by next-generation sequencing technology.

Results The α-diversity of the intestinal microbiota of cesarean delivery neonates was significantly lower than that of the naturally delivered neonates on the 28th day (p = 0.005). After supplementation with probiotics for 28 days, the α-diversity and the β-diversity of the gut flora in the cesarean-born infants (CDL28 and CDH28) was similar to that in the vaginally delivery infants. Meanwhile, the abundances of Lactobacillus and Bifidobacterium were significantly increased since the 3rd day of probiotic supplementation. Besides, the sustained supplementation of probiotics to neonates would help improve the abundance of the operational taxonomic units in several different Clusters of Orthologous Groups of proteins.

Conclusion This study showed that probiotics supplementation to cesarean-born neonates since birth might impact the diversity and function of gut microbiota.

Key Points

  • Cesarean-born neonates

  • Probiotic supplementation impact gut flora

  • Bifidobacterium and Lactobacillus

Keywords

neonates - cesarean - probiotics - intestinal microbiota - 16S rRNA

Ethical Approval

This project was approved by the Ethics Committee of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2017–157), and informed consent was obtained from parents.


Note

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.


Authors' Contributions

W.Y. and J.Y. conceived the study design. J.L. was responsible for the recruitment and collection of samples. W.Y. and L.T. performed the data analysis and completed the initial manuscript. J.Y. revised the manuscript. All the authors read and approved the final version of the manuscript.


Supplementary Material



Publication History

Received: 23 September 2019

Accepted: 13 April 2020

Article published online:
23 May 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 WHO. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. 2001; October:1–34
    PubMed
  • 2 Collins MD, Gibson GR. Probiotics, prebiotics, and synbiotics: approaches for modulating the microbial ecology of the gut. Am J Clin Nutr 1999; 69 (05) 1052S-1057S
    CrossrefPubMedGoogle Scholar
  • 3 Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science 2016; 352 (6285): 539-544
    CrossrefPubMedGoogle Scholar
  • 4 Hansen CH, Nielsen DS, Kverka M. et al. Patterns of early gut colonization shape future immune responses of the host. PLoS One 2012; 7 (03) e34043
    CrossrefPubMedGoogle Scholar
  • 5 Sommer F, Bäckhed F. The gut microbiota--masters of host development and physiology. Nat Rev Microbiol 2013; 11 (04) 227-238
    CrossrefPubMedGoogle Scholar
  • 6 Kalliomäki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr 2008; 87 (03) 534-538
    CrossrefPubMedGoogle Scholar
  • 7 Subramanian S, Huq S, Yatsunenko T. et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 2014; 510 (7505): 417-421
    CrossrefPubMedGoogle Scholar
  • 8 Qin J, Li Y, Cai Z. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490 (7418): 55-60
    CrossrefPubMedGoogle Scholar
  • 9 Gevers D, Kugathasan S, Denson LA. et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 2014; 15 (03) 382-392
    CrossrefPubMedGoogle Scholar
  • 10 Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med 2016; 22 (07) 713-722
    CrossrefPubMedGoogle Scholar
  • 11 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 (26) 11971-11975
    CrossrefPubMedGoogle Scholar
  • 12 Dominguez-Bello MG, De Jesus-Laboy KM, Shen N. et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 2016; 22 (03) 250-253
    CrossrefPubMedGoogle Scholar
  • 13 Bäckhed 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 (05) 690-703
    CrossrefPubMedGoogle Scholar
  • 14 Madan JC, Hoen AG, Lundgren SN. et al. Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. JAMA Pediatr 2016; 170 (03) 212-219
    CrossrefPubMedGoogle Scholar
  • 15 Yassour M, Vatanen T, Siljander H. et al; DIABIMMUNE Study Group. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 2016; 8 (343) 343ra81
    CrossrefPubMedGoogle Scholar
  • 16 Nagpal R, Tsuji H, Takahashi T. et al. Ontogenesis of the gut microbiota composition in healthy, full-term, vaginally born and breast-fed infants over the first 3 years of life: a quantitative bird's-eye view. Front Microbiol 2017; 8: 1388-1388
    CrossrefPubMedGoogle Scholar
  • 17 Munyaka PM, Khafipour E, Ghia JE. External influence of early childhood establishment of gut microbiota and subsequent health implications. Front Pediatr 2014; 2: 109-109
    CrossrefPubMedGoogle Scholar
  • 18 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 (04) 629-633
    CrossrefPubMedGoogle Scholar
  • 19 Bager P, Wohlfahrt J, Westergaard T. Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy 2008; 38 (04) 634-642
    CrossrefPubMedGoogle Scholar
  • 20 Cardwell CR, Stene LC, Joner G. et al. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia 2008; 51 (05) 726-735
    CrossrefPubMedGoogle Scholar
  • 21 Pei Z, Heinrich J, Fuertes E. et al; Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus Air Pollution and Genetics (LISAplus) Study Group. Cesarean delivery and risk of childhood obesity. J Pediatr 2014; 164 (05) 1068-1073.e2
    CrossrefPubMedGoogle Scholar
  • 22 Fujimura KE, Sitarik AR, Havstad S. et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med 2016; 22 (10) 1187-1191
    CrossrefPubMedGoogle Scholar
  • 23 Penders J, Thijs C, van den Brandt PA. et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 2007; 56 (05) 661-667
    CrossrefPubMedGoogle Scholar
  • 24 Madan JC, Salari RC, Saxena D. et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 2012; 97 (06) F456-F462
    CrossrefPubMedGoogle Scholar
  • 25 Mai V, Torrazza RM, Ukhanova M. et al. Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants. PLoS One 2013; 8 (01) e52876
    CrossrefPubMedGoogle Scholar
  • 26 Cernada M, Bäuerl C, Serna E, Collado MC, Martínez GP, Vento M. Sepsis in preterm infants causes alterations in mucosal gene expression and microbiota profiles compared to non-septic twins. Sci Rep 2016; 6 (01) 25497-25497
    CrossrefPubMedGoogle Scholar
  • 27 Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol 2013; 6 (01) 39-51
    CrossrefPubMedGoogle Scholar
  • 28 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 (01) 2-10
    CrossrefPubMedGoogle Scholar
  • 29 Brüssow H. How stable is the human gut microbiota? And why this question matters. Environ Microbiol 2016; 18 (09) 2779-2783
    CrossrefPubMedGoogle Scholar
  • 30 Rodríguez 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 (01) 26050-26050
    PubMedGoogle Scholar
  • 31 Shao Y, Forster SC, Tsaliki E. et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature 2019; 574 (7776): 117-121
    CrossrefPubMedGoogle Scholar
  • 32 La Fata G, Weber P, Mohajeri MH. Probiotics and the gut immune system: indirect regulation. Probiotics Antimicrob Proteins 2018; 10 (01) 11-21
    CrossrefPubMedGoogle Scholar
  • 33 Lewis ZT, Mills DA. Differential establishment of bifidobacteria in the breastfed infant gut. Nestle Nutr Inst Workshop Ser 2017; 88: 149-159
    CrossrefPubMedGoogle Scholar
  • 34 Milani C, Lugli GA, Duranti S. et al. Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut. Sci Rep 2015; 5 (01) 15782-15782
    CrossrefPubMedGoogle Scholar
  • 35 Frese SA, Hutton AA, Contreras LN. et al. Persistence of supplemented Bifidobacterium longum subsp. infantis EVC001 in breastfed infants. MSphere 2017; 2 (06) e00501-17
    CrossrefPubMedGoogle Scholar
  • 36 Korpela K, Salonen A, Vepsäläinen O. et al. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants. Microbiome 2018; 6 (01) 182
    CrossrefPubMedGoogle Scholar
  • 37 Liu Y, Qin S, Song Y. et al. The perturbation of infant gut microbiota caused by cesarean delivery is partially restored by exclusive breastfeeding. Front Microbiol 2019; 10: 598
    CrossrefPubMedGoogle Scholar
  • 38 Stokholm J, Thorsen J, Chawes BL. et al. Cesarean section changes neonatal gut colonization. J Allergy Clin Immunol 2016; 138 (03) 881-889.e2
    CrossrefPubMedGoogle Scholar
  • 39 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 (02) 198-211
    CrossrefPubMedGoogle Scholar
  • 40 Kang HJ, Im SH. Probiotics as an immune modulator. J Nutr Sci Vitaminol (Tokyo) 2015; 61 (Suppl): S103-S105
    CrossrefPubMedGoogle Scholar