The use of antibiotics to prevent transmission of Group B Streptococcus to vaginally born babies seems to reduce the bacterial diversity of the infant gut microbiome.

 

Does Antibiotic Use or Birth Mode Influence Infant Microbiomes?

Vaginal birth is thought to convey a higher diversity of bacteria to newborn babies than cesearean section deliveries [1-4]. However, antibiotics are routinely used during c-sections to prevent infection. Antibiotic use may be what decreases bacterial diversity, not c-sections. Mothers positive for Group B Strep (GBS) giving birth naturally receive antibiotics too. Called intrapartum antibiotic prophylaxis (IAP), specific CDC guidelines for ampicillin doses and timing are established for GBS+ mothers. The antibiotic crosses the placenta and will be at active doses in the serum and amniotic fluids. Infants born vaginally to mothers given antibiotics have been found to have a different microbiome than vaginally born infants without antibiotic exposure, but these results could also be due to the methods used for the study, more on that another time.

 

IAP Reduced Group B Strep and Bacterial Diversity

In this study [5], ten Infants born vaginally to mother’s given antibiotics had lower levels of Actinobacteria and Bacteroidetes and higher amounts of Proteobacteria than the ten babies not exposed to antibiotics. So what does this mean? These are similar results to previous studies. Fewer Bifidobacterium longum subspecies infantis and more Enterobacteriaceae correlates with increased allergic status [6, 7]. Thus the use of IAP with vaginal birth may explain why some vaginally born babies have increased allergy issues. IAP vaginally born babies may have a disrupted gut microbiome. While the microbiome diversity studies are correlated with allergic conditions, they are beginning observations that can be used for to design hypotheses for future studies.

 

Group B Strep
Intrapartum Antibiotic Prophylaxis (IAP) use kills Group B Streptococcus (the chain of round bacteria), but also may kill off beneficial bacteria such as Bifidobacterium (purple) and allow Enterobacteraceae (orange rods with flagella) to increase.

Follow up Studies with Breastfeeding?

Examining larger sample sizes of infants and following IAP and control babies that are exclusively breastfed, have mixed feeding regimes, and formula fed is warranted. Exclusive breastfeeding for 3 months in c-section IAP babies has shown an increase in Bifidobacterium sp. [2] Are all of the mom’s beneficial bacteria being transmitted, but at lower amounts the bacterial types could be adjusted with foods? Breast milk has been found to decrease Enterobacteriacea in infant feces and Bifidobacterium sp. increase [8]. The sugars (oligosaccharides) found in breast milk can’t be digested by most bacteria. Bifidobacterium longum subspecies infantis does feed and grow on human milk oligosaccharides [8-10], so perhaps we can “feed the helpful bacteria and starve the less helpful/harmful bacteria”.

Group B Strep
Does the presence of human milk sugars found in breast milk select for survival of Bifidobacterium infantis (purple with baby bonnet), while starving Enterobacteraceae (orange rod)?

V4 Ideal Region of 16S rRNA for Infant Gut Microbiome Analysis

In addition to the IAP findings, this paper suggests that the V4 region of the 16S rRNA gene best identifies the broadest diversity of bacterial types in the infant gut. Thus, primer choice and region of the 16S rRNA investigated should be carefully considered. While this isn’t the first paper to warn about primer choice, it is good to see that they did explicitly see how primer choice changed bacteria identified in the infant gut.

 

Paper Critique

Weaknesses:

  • Small sample size
  • Information on mom’s vaginal and gut microbiome would have strengthened the claims

Strengths:

  • Antibiotic type and doses well controlled
  • Amplification of multiple sets of 16S rRNA variable regions to best identify the infant gut bacterial diversity.

 

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REFERENCES

 

  1. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Chari RS, Sears MR, Becker AB, Scott JA, Kozyrskyj AL: Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. Canadian Medical Association Journal 2013, 185(5):385-394.
  2. Azad MB, Konya T, Persaud RR, Guttman DS, Chari RS, Field CJ, Sears MR, Mandhane PJ, Turvey SE, Subbarao P et al: Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG: An International Journal of Obstetrics & Gynaecology 2015.
  3. Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, Li Y, Xia Y, Xie H, Zhong H et al: Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host & Microbe 2015, 17(5):690-703.
  4. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N: 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.
  5. Aloisio I, Quagliariello A, De Fanti S, Luiselli D, De Filippo C, Albanese D, Corvaglia LT, Faldella G, Di Gioia D: Evaluation of the effects of intrapartum antibiotic prophylaxis on newborn intestinal microbiota using a sequencing approach targeted to multi hypervariable 16S rDNA regions. Appl Microbiol Biotechnol 2016:1-10.
  6. He F, Ouwehand AC, Isolauri E, Hashimoto H, Benno Y, Salminen S: Comparison of mucosal adhesion and species identification of bifidobacteria isolated from healthy and allergic infants. FEMS Immunology & Medical Microbiology 2001, 30(1):43-47.
  7. Björkstén B, Sepp E, Julge K, Voor T, Mikelsaar M: Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001, 108(4):516-520.
  8. Underwood MA, German JB, Lebrilla CB, Mills DA: Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res 2015, 77(1-2):229-235.
  9. Sela DA, Chapman J, Adeuya A, Kim JH, Chen F, Whitehead TR, Lapidus A, Rokhsar DS, Lebrilla CB, German JB et al: The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proceedings of the National Academy of Sciences 2008, 105(48):18964-18969.
  10. Wang M, Li M, Wu S, Lebrilla CB, Chapkin RS, Ivanov I, Donovan SM: Fecal microbiota composition of breast-fed infants is correlated with human milk oligosaccharides consumed. J Pediatr Gastroenterol Nutr 2015, 60(6):825-833.
  11. Scheffers D-J, Pinho MG: Bacterial Cell Wall Synthesis: New Insights from Localization Studies. Microbiol Mol Biol Rev 2005, 69(4):585-607.

 

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