Ishizeki S, Sugita M, Takata M, Yaeshima T: Effect of administration of bifidobacteria on intestinal microbiota in low-birth-weight infants and transition of administered bifidobacteria: A comparison between one-species and three-species administration. Anaerobe 2013, 23(0):38-44. In this study the investigators report 3 sequential periods in their NICU, one without probiotics, one with one strain of bifidobacteria (breve) and one with 3 strains of bifidobacteria (breve, infantis and longum). They gave 5 x 108 bugs for each strain so the last group got 3 times as many. The babies were 1 to 2 kg and feeding by 7 days of age, and got the germs for 6 weeks. They looked at the microbiome with culture rather than molecular techniques and found there was better bowel colonization with bifidobacteria when the mixture was used than the single strain. Also there were fewer clostridia when either probiotic regime was used, and fewer enterobacteriaceae with the mixture. It was a small study with about 14 babies per group, so no clinical differences would be expected.
Serce O, Benzer D, Gursoy T, Karatekin G, Ovali F: Efficacy of saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: A randomised controlled trial. Early Human Development 2013. This is the second published randomized study of saccharomyces, a probiotic yeast, in preterm infants, showing no benefit on NEC or sepsis. This could be a problem of power, as there were ‘only’ 208 babies in the trial and a lowish rate of NEC (7%) but it looks like we shouldn’t bother investigating single-strain probiotic administration with this yeast any further. I believe there is another trial that has been presented but not published as yet, also showing no benefit, but I don’t know any details.
Westerbeek EAM, Slump RA, Lafeber HN, Knol J, Georgi G, Fetter WPF, Elburg RM: The effect of enteral supplementation of specific neutral and acidic oligosaccharides on the faecal microbiota and intestinal microenvironment in preterm infants. Eur J Clin Microbiol Infect Dis 2013, 32(2):269-276. This was an RCT of prebiotic supplementation with the molecules noted in the title. They found that prebiotics in the milk did indeed increase intestinal colonization in 113 VLBW infants, compared to placebo. The biggest effect though was the use of broad spectrum antibiotics, which wreck all the bugs in the gut.
Gupta RW, Tran L, Norori J, Ferris MJ, Eren AM, Taylor CM, Dowd SE, Penn D: Histamine-2 receptor blockers alter the fecal microbiota in premature infants. Journal of Pediatric Gastroenterology & Nutrition 2013, 56(4):397-400. A case control study of infants from a prospective evaluation of normal microbiome development in the preterm. Of the 76 babies in the study there were 25 who had received H2 blockers for a mean of 19 days before the stool sample. None of them had recently received antibiotics. The babies that were on H2 blockers had less bacterial diversity, more Proteobacteria (some of which are bad) and fewer Firmicutes (some of whom are good, including lactobacillae). The authors don’t talk about the Actinobacteria which includes Bifidobacteria.
As the authors state:
Many Proteobacteria, especially of the family Enterobacteriaceae, are known pathogens, such as Klebsiella, Shigella, Escherichia coli, Citrobacter … They are Gram-negative, facultative anaerobes, often motile, and capable of producing toxins, adhesins, and capsular antigens. They have the ability to undergo antigenic phase variation, type III secretion, and exchange antimicrobial resistance genes. Some have been associated with epidemics or anecdotal cases of NEC. An overabundance of such organisms in an immature GI tract is cause for concern.
I was happy to note tonight doing rounds, that, as usual, there isn’t a single preterm infant in the intensive care part of my unit who is receiving an H2blocker, or a PPI. Gastric acid is there for good reasons.