This month, Annika Tiit-Vesingi from the University of Tartu, Estonia, is reviewing:
Van Rossum T, Haiß A, Knoll RL, et al. Bifidobacterium and Lactobacillus Probiotics and Gut Dysbiosis in Preterm Infants: The PRIMAL Randomized Clinical Trial. JAMA Pediatr. 2024;178(10):985-995.
Why is this important?
The impact of probiotic treatments on the growth of resistant bacteria (MDRO+) and the early development of the microbiome in preterm infants is still not fully understood. While the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommends using multistrain probiotics to lower the risk of necrotizing enterocolitis (NEC), the American Academy of Pediatrics (AAP) does not support routine probiotic use in preterm infants due to concerns about contamination with supplements.
What was done in this study?
The PRIMAL (Priming Immunity at the Beginning of Life) randomized clinical study conducted in 18 level III NICUs in Germany between April 2018 and June 2020, included premature infants with gestational age of 28+0 to 32+6 weeks. Participants were block randomized to probiotics (Bifidobacterium longum subsp infantis, Bifidobacterium animalis subsp lactis, and Lactobacillus acidophilus) or placebo (cornstarch powder) within 48 hours after birth over 28 days. Stool samples were collected on days 3 and 30 for MDRO+ screening and microbiome analysis. Clinical metadata were recorded on days 3, 30, and at discharge, with follow-up at 6, 12, and 24 months.
What was observed?
In 618 preterm infants, probiotic use did not reduce MDRO+ colonization. Safety outcomes (late-onset sepsis and severe gastrointestinal complications) were similar between groups. Probiotic strains were frequently acquired by infants in the placebo group within the hospital environment. Probiotic treatment shifted the microbiome composition towards eubiosis patterns commonly found in healthy full-term infants, and the B infantis probiotic strain was the main driver of eubiosis or normative gut microbiome maturation.
Key take away points
This study highlights the importance of understanding the interaction of different factors, such as microbiome-modulating treatments (like probiotics), the hospital environment, and patient outcomes, to improve interventions. B. infantis was the most commonly acquired probiotic strain in the placebo-treated group, suggesting that the microbiome barriers between individuals may be particularly low for this species. The finding implies that microbial strains may have different transmission rates, which is important for understanding how microbial communities (endemic flora) behave in neonatal units.