Necrotizing Enterocolitis: manipulating the microbiome, part 2

The Newcastle, UK, group has published an article about the intestinal microbiome of babies receiving routine probiotic prophylaxis. Abdulkadir B, et al. Routine Use of Probiotics in Preterm Infants: Longitudinal Impact on the Microbiome and Metabolome. Neonatology. 2016;109(4):239-47. The authors studied 7 extremely premature babies who received Infloran (Bifidobaterium bifidum, and Lactobacillus acidophilus) and 3 controls, also extremely premature.

Basically, they showed greater Bifidobacterium (15.1%) and Lactobacillus (4.2%) during supplementation compared to the control group (4.0% and 0%, respectively). Bifidobacterium counts stayed high following discharge, but the Lactobacillus disappeared.

Several previous studies in very preterm infants have shown extremely low, or absent, Bifidobacterial colonies, increasing that to 15% shows an enormous change in the intestinal microbiome.

The impacts of the microbiome changes on the “metabolome” of gut are also presented, the results seem to me preliminary, and as yet of uncertain significance, but there appear to be some differences between babies getting probiotics and those not.

Some of the same authors have written a review article Embleton ND, et al. Probiotics for prevention of necrotizing enterocolitis and sepsis in preterm infants. Curr Opin Infect Dis. 2016;29(3):256-61.  It is fairly brief and summarizes the data well, the abstract ends like this:

Despite current uncertainties, it is difficult for clinicians to ignore the current data, and increasing numbers now use commercially available products. It remains a matter of concern that many products lack the robust quality control most clinicians and parents would consider important for use in vulnerable populations. Head-to-head trials are needed.

Which I think is right on the money. And also brings me neatly to the next article:

Lewis ZT, et al. Validating bifidobacterial species and subspecies identity in commercial probiotic products. Pediatr Res. 2016;79(3):445-52. Mark Underwood’s group from UCDavis examined the composition of 16 formulations of probiotics that were promoted as containing Bifidobacteria, some available on-line, and others in local stores. One of the complicating factors in this field is the changes in classification that occur, so the same strain can go from being an B. longum to being a B. animalis.

They found that the advertised content of many of the products varied significantly from the true composition. Only 1 of the 16 products tested had exactly the same Bifidobacteria species in every sample as what was written on the label. In addition:

Some products were not internally consistent as both pill-to-pill and lot-to-lot variation were observed

Some producers in other parts of the world have better quality control, and more reliable composition, but it is really hard to know,if you just go to the local health food store, if you are getting what you think.

When we started using probiotics routinely a few years ago, we were fortunate that there were preparations with good quality control, and which followed GMP. Standards for probiotics for premies are extremely important.

Mark Underwood is also an author of a recent review article, Vongbhavit K, Underwood MA. Prevention of Necrotizing Enterocolitis Through Manipulation of the Intestinal Microbiota of the Premature Infant. Clin Ther. 2016;38(4):716-32. Another excellent review, the last sentence in their abstract is the following :

Shaping the intestinal microbiota of the premature infant through human milk feeding and dietary supplements decreases the risk of NEC. Further studies to identify the ideal microbial composition and the most effective combination of supplements are indicated.

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.

2 Responses to Necrotizing Enterocolitis: manipulating the microbiome, part 2

  1. Thank you for two very nice posts.

    The potential effects of manipulating the microbiome are vast and fascinating. Possible effects reach far beyond NEC protection – also (especially ?) in the very preterm.

    Science has devoted an entire recent special issue to the subject of Manpulating the Microbiota.
    http://science.sciencemag.org/content/352/6285
    It is highly recommendable.
    As the neonatal community move forward in this area, should we contemplate the need to examine other outcomes than “just” NEC/sepsis ? The obvious ones could be long term effects such as risk of asthma/allergy and recurrent infections, but short term outcomes could be considered. At least an effect on nutritional status (ie weight gain) seems plausible ?

    • I think you are likely to be right there is certainly evidence form the RCTs that feeding tolerance is improve with probiotics, in those trials that have reported the outcome it is usually improved. Unfortunately there is no uniform definition of feeding tolerance, so it is difficult to put the data together. Other benefits are certainly possible also.

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