A recent study in Nature Communications reveals that probiotics can help very-low-birth-weight (VLBW) preterm infants resist antibiotic-resistant bacteria, offering a potential lifeline for one of the most vulnerable populations in neonatal care.
Background
Approximately one in ten babies is born prematurely, and VLBW infants—those weighing under 1,500 grams—face significant health risks. In Neonatal Intensive Care Units (NICUs), broad-spectrum antibiotics are critical for survival but can disrupt the gut microbiome, which is essential for developing immunity and suppressing harmful bacteria.
The World Health Organization recommends probiotics containing specific bacterial strains for very preterm, exclusively human milk-fed infants, raising the question of whether routine probiotic supplementation can counterbalance antibiotic-related risks.
Study Design
Researchers conducted a controlled sub-study as part of the Baby-Associated Microbiota of the Intestine (BAMBI) observational cohort, following 34 VLBW preterm infants under 33 weeks’ gestation.
Infants were exclusively fed human or donor breast milk and divided into two groups: one received probiotics (Bifidobacterium bifidum and Lactobacillus acidophilus, brand name Infloran®), and the other did not. Some infants in both groups received short-term antibiotics, while others did not.
Weekly fecal samples over the first three weeks were analyzed using shotgun metagenomic sequencing and strain-level genome reconstruction to track microbial composition and antibiotic resistance genes (ARGs).
Key Findings
Probiotic supplementation led to gut communities dominated by Bifidobacterium, actively replicating and supporting colonization resistance. Non-supplemented infants, in contrast, showed higher levels of early-life pathobionts, including Klebsiella, Escherichia, Enterococcus, and Staphylococcus.
Beneficial species such as Bifidobacterium breve and Bifidobacterium longum appeared earlier and in greater abundance in the probiotic group.
Infants receiving probiotics carried fewer ARGs across multiple drug classes. Notably, resistance to critical antibiotics such as fluoroquinolones and colistin was found only in non-supplemented infants.
One non-supplemented sample even contained the colistin-resistance gene mcr-9.1, suggesting the hidden circulation of last-resort resistance determinants. Short-term antibiotic use slightly altered microbial composition but did not dramatically reduce diversity.
Strain-level analyses revealed that Enterococcus, Escherichia, Klebsiella, and Staphylococcus harbored the highest ARG loads. Nearly half of non-supplemented Escherichia strains were multidrug-resistant, while none in the probiotic group met this threshold.
Horizontal gene transfer events, which can spread resistance, were more frequent after antibiotic exposure. Laboratory models confirmed that resistance genes could transfer between Enterococcus strains in the infant gut, highlighting the ongoing risk of antibiotic-driven resistance spread.
Conclusions
Probiotic supplementation in VLBW preterm infants promotes beneficial, Bifidobacterium-rich gut communities, reduces ARG burden, and limits multidrug-resistant features.
However, Enterococcus persists as a key reservoir for resistance, and even short antibiotic courses increase the risk of gene transfer. Pairing evidence-based probiotics with careful antibiotic stewardship and strict infection control measures can enhance protection for these vulnerable infants.
Further research is needed to optimize probiotic strains, dosing, and duration to maximize benefits while minimizing resistance risks. For NICUs and families, aligning feeding practices, hygiene, and antibiotic use is essential to safeguard fragile newborns.
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