Prebiotics, Probiotics and the microbiome

A series of interesting recent articles:

Yang J, et al. Application of Laser Capture Microdissection and 16S rRNA Gene Polymerase Chain Reaction in the Analysis of Bacteria Colonizing the Intestinal Tissue of Neonates With Necrotizing Enterocolitis. Pediatr Infect Dis J. 2015;34(10):e279-89. These investigators examined intestinal samples resected during NEC surgery. Some controls with intestinal atresia were also studied. They were able to examine bacteria specifically related to the NEC tissue samples. They found several groups of bugs that were not present in the controls. Enterococcus sp. and Escherichia sp. were frequently found in both infants with NEC and controls, whereas Pseudomonas sp., Klebsiella sp., Acinetobacter sp., Clostridium sp., Ochrobactrum sp. and Arcobacter sp. were detected only in NEC tissue samples. In contrast to other studies they actually showed more bacterial diversity in the NEC babies than the controls, but that may be because of the nature of the controls, the controls had intestinal atresia, so they would all have to be very young, and the control tissue all came from the small intestine, whereas the NEC tissue was from large intestine, with some samples from the small.

Carl MA, et al. Sepsis from the gut: the enteric habitat of bacteria that cause late-onset neonatal bloodstream infections. Clinical infectious diseases. 2014;58(9):1211-8. This study report is difficult to interpret, which is a shame as it seems fascinating. The authors don’t say when they started collecting stools, nor how frequently, but they did find, in many infants who subsequently developed sepsis, that stools that had been collected beforehand were often colonized with organisms which seem identical to the organisms that they isolated from the blood. Those organisms included E coli (2) Serratia (2) and 3 cases of late onset sepsis caused by GBS (which is an unusually high proportion). A sepsis caused by Klebsiella and 2 MRSA were not preceded by intestinal colonization, and another baby had GBS colonization and was infected by a different GBS. Babies who did not develop sepsis did not have these particular organisms. The authors don’t say much about the microbiome of the non-septic babies.

How can we try and get our babies colonized with the good bugs?

Skin to skin contact with the baby’s mother, that’s how. Hendricks-Munoz KD, et al. Skin-to-Skin Care and the Development of the Preterm Infant Oral Microbiome. American journal of perinatology. 2015(EFirst). They showed associations between skin to skin care and development of the microbiome of the babies’ saliva, with “an accelerated pace of oral microbial repertoire maturity”.

Also don’t give them (or their mothers) antibiotics. Arboleya S, et al. Intestinal Microbiota Development in Preterm Neonates and Effect of Perinatal Antibiotics. The Journal of pediatrics. 2014(0). Because, the infants not exposed to antibiotics (either directly or via their mothers) had higher relative amounts of Comamonadaceae, Staphylococcaceae, and unclassified Bacilli . Infants not exposed to antibiotics also had significantly higher percentages of Bifidobacteriaceae, Streptococcaceae, unclassified Actinobacteria, and unclassified Lactobacillales and lower of Enterobacteriaceae than both groups of infants whose mothers received antibiotics.

Also give them human milk, its packed with goodies.

Underwood MA, et al. Human Milk Oligosaccharides in Premature Infants: Absorption, Excretion and Influence on the Intestinal Microbiota. Pediatr Res. 2015. Or at least it is if your mother is not a non-secretor. It seems that some mothers are homozygous for a gene that prevents them secreting fucosylated glycans into their breast milk. It also looks like this is quite common, 6 out of 1 mothers in this study were non-secretors, and this status had a big influence on the intestinal microbiome development. Also the sialylated oligosaccharides were very variable and some mothers produced milk that had oligosaccharides with little fucose or sialic acid.; those mothers’ babies had more dysbiosis than the others.

So choose your mother carefully if you are going to be born prematurely.

Barrett E, et al. The neonatal gut harbours distinct bifidobacterial strains. Archives of disease in childhood Fetal and neonatal edition. 2015. In this study from healthy full term infants they identified over 170 different bifidobacteria strains. Some of the babies were being breast fed, some receiving a formula without prebiotics, and some a formula with added prebiotics. In this case the prebiotics were galacto-oligosaccharides and poly-fructose. They showed that dietary prebiotic supplementation was associated with an increased prevalence of B. longum in infants in addition to increased strain diversity
Endo A, et al. Long-term monitoring of the human intestinal microbiota from the 2nd week to 13 years of age. Anaerobe. 2014;28(0):149-56. Ten subjects donated stool on multiple occasions during the first 13 years of their lives. They changed. Most of the change was in the first 12 months of life. The major changes were int eh relative abundance of the families of bugs, major species did not change dramatically. Probiotic supplementation in early life didn’t seem to have a lasting effect on the microbiome.

Hickey L, et al. Cross-colonization of infants with probiotic organisms in a neonatal unit. Journal of Hospital Infection. 2014;88(4):226-9. In this data from the ProPrems trial, only 3 of the 38 controls tested were cross-colonized with the probiotics they were testing. Which is lower than some other studies, maybe in Melbourne they are better at washing their hands.

And finally, two very nice review articles covering the issues.

Walker WA, Iyengar RS. Breast milk, microbiota, and intestinal immune homeostasis. Pediatr Res. 2015;77(1-2):220-8.

Pacheco AR, et al. The Impact of the Milk Glycobiome on the Neonate Gut Microbiota. Annual Review of Animal Biosciences. 2015;3(1):419-45.


About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , , . Bookmark the permalink.

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