Rao S, et al. Probiotic supplementation in neonates with congenital gastrointestinal surgical conditions: a pilot randomised controlled trial. Pediatr Res. 2022. When we started using probiotics there had been a couple of case reports of probiotic associated sepsis in infants with congenital GI anomalies, specifically omphalocoele, so we decided to not include them in our probiotic protocol. I was never too sure that was the right thing to do, especially as infants with gastroschisis in particular are at high risk of NEC. The group from Perth, Western Australia, randomized 61 babies to a Bifidobacterium mixture (B. breve, B. longum longum, and B longum infantis) or placebo and followed their intestinal microbiome development weekly until discharge, they found that there was a progressive change in the microbiome due to supplementation, with less dysbiosis, specifically a lower abundance of potential pathogens (Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Pseudomonadaceae, Staphylococcaceae, Streptococcaceae &Yersineaceae) and much more Bifidobacteria. In a pilot study of this size one wouldn’t necessarily expect to see a clinical impact, although growth parameters were improved with probiotics, in particular head growth; or rather, the postnatal growth restriction, was less severe in the probiotic growth.

Plummer EL, et al. The effect of probiotic supplementation on the gut microbiota of preterm infants. J Med Microbiol. 2021;70(8). This study analysed the intestinal microbiomes of infants randomized in the ProPrems trial, which was a large multicentre trial of a mixture of B longum infantis, B animalis lactis and Streptococcus thermophilus vs placebo. 99% of the babies in the probiotic group had the Bifidobacterial DNA in their stools during treatment, but in only about 90% of the fecal samples, about 20% to 35% of the controls also had the bacteria in their stools at times. The relative abundance of the B infantis was quite variable, suggesting we need to find ways to make colonization more effective.

Hui Y, et al. The effect of early probiotic exposure on the preterm infant gut microbiome development. Gut Microbes. 2021;13(1):1951113. This is a study of microbiome development in 2 cohorts of preterms, before and after routine probiotic use (a mixture of Lacticaseibacillus rhamnosus GG, the bacterium formerly known as Prince Lactobacillus, and Bifidobacterium animalis ssp. lactis) in Copenhagen. They showed less impact on the progression of microbiome changes than some other studies, associated with a variable abundance of the probiotic organisms, but did show an impact leading to a reduction in Klebsiella concentrations in the stools.

Fleming P, et al. Bifidobacterium breve BBG-001 and intestinal barrier function in preterm babies: Exploratory Studies from the PiPS Trial. Pediatr Res. 2021;89(7):1818-24. This is an analysis of microbiome impacts and intestinal functional impacts of the B breve used in the PiPs trial. In addition to the usual 16sRNA, they also cultured the stools, and found they were able to grow Bifidobacteria, identified by pcr as B. breve, from most of the probiotic babies, as well as some controls, but found that babies colonised with B breve actually had more potentially pathogenic Enterobacteriacae from 3 weeks onwards. They did not see a benefit on intestinal barrier function of the probiotic.

Overall, I think these recent studies imply that the best probiotic to have an impact on the preterm infant microbiome, and, as a result on NEC, is Bifidobacterium Longum subsp. Infantis. Other data from network meta-analysis that I have discussed previously, is also consistent with this, and also consistent with a benefit of a mixture of Bifidobacteria (most mixtures include B infantis). Ways of ensuring good colonisation, such as the addition of prebiotics, especially Human Milk Oligosaccharides, and provision of human milk will probably help to ensure the greatest benefit.