Probiotics Show Promise in Curbing Antibiotic Resistance in Premature Infants, Study Finds
A new study published in Nature Communications reveals that probiotic supplementation can significantly reduce the burden of drug-resistant bacteria in premature babies, though antibiotics continue to drive the spread of resistance genes, highlighting the urgent need for safer treatment strategies in Neonatal Intensive Care Units (NICUs).
A growing threat to vulnerable newborns, antibiotic resistance is a complex issue demanding innovative solutions. Researchers are now exploring the potential of probiotics to mitigate some of the risks associated with antibiotic use in this fragile population.
The Fragility of Premature Infants and the Antibiotic Dilemma
Approximately one in ten babies is born prematurely, and very-low-birth-weight (VLBW) infants – those under 1500g – face a particularly challenging start to life. In NICUs, broad-spectrum antibiotics are often lifesaving, but they can also disrupt the delicate gut microbiome, which plays a crucial role in developing immunity and warding off harmful microbes. The World Health Organization (WHO) recommends probiotics for very preterm infants exclusively fed human milk, raising the question of whether routine probiotic use can counteract the negative effects of antibiotics. Hospitals are also grappling with increasing rates of multidrug-resistant (MDR) infections, posing a serious danger to these vulnerable newborns.
Unpacking the Gut Microbiome and the Resistome
A recent study, conducted by researchers from the Baby-Associated Microbiota of the Intestine (BAMBI) observational cohort, investigated the impact of early antibiotic exposure and probiotic supplementation on the gut microbiome, antibiotic resistance genes (ARGs), and the dynamics of MDR pathogens in 34 VLBW preterm infants. The infants, all exclusively fed human milk or donor breastmilk and under 33 weeks’ gestation, were divided into two groups: one receiving probiotic supplementation (specifically Bifidobacterium bifidum and Lactobacillus acidophilus [Infloran®]) and a control group that did not. Within each group, some infants received short courses of antibiotics (benzylpenicillin and/or gentamicin for a median of 3 days), while others did not. Researchers collected weekly fecal samples over three weeks, utilizing advanced genomic sequencing to track changes in the gut microbiome and the spread of antibiotic resistance.
Probiotics Foster Beneficial Bacteria, Reduce Resistance
The study revealed a significant difference between the two groups. The probiotic-supplemented cohort saw a dominance of Bifidobacterium, driven by the administered probiotics, with evidence of active replication. In contrast, the non-supplemented cohort exhibited a higher prevalence of potentially harmful bacteria, including Klebsiella, Escherichia, Enterococcus, and Staphylococcus. Beneficial infant-associated species, such as Bifidobacterium breve and Bifidobacterium longum, also appeared earlier and in greater abundance in the probiotic group, aligning with the utilization of human milk oligosaccharides and enhanced colonization resistance.
Importantly, infants receiving probiotics carried fewer ARGs and fewer classes of resistance genes compared to those who did not. While genes conferring resistance to common antibiotics like aminoglycosides and beta-lactams were prevalent in both groups, resistance to fluoroquinolones and colistin was largely confined to the non-supplemented infants. Researchers even identified a colistin resistance gene, mcr-9.1, in one non-supplemented sample – a finding that predated its formal discovery and underscores the hidden circulation of last-resort antibiotic resistance determinants.
Antibiotics Still Pose a Risk, Horizontal Gene Transfer Remains a Concern
While short courses of antibiotics did not drastically alter the overall diversity of the gut microbiome, they were associated with an early increase in Klebsiella or Enterococcus. Correlation analyses showed a clear link: higher Bifidobacterium abundance correlated with fewer ARGs, while higher levels of Enterococcus and Staphylococcus were associated with increased ARG loads. Enterococcus, Escherichia, Klebsiella, and Staphylococcus were identified as carrying the most substantial resistance portfolios.
Furthermore, the study demonstrated that even short antibiotic courses increased the likelihood of horizontal gene transfer (HGT) – the process by which bacteria share genetic material, including resistance genes. Researchers observed related Enterococcus strains circulating among unrelated infants within the same hospitals, suggesting nosocomial transmission. An ex vivo experiment confirmed that a plasmid carrying an aminoglycoside resistance gene could transfer from Enterococcus faecium to a recipient strain, conferring gentamicin resistance.
A Path Forward: Probiotics and Antibiotic Stewardship
In conclusion, the study demonstrates that probiotic supplementation can foster a gut microbiome rich in Bifidobacterium, reduce the burden of ARGs, and limit the development of MDR features in VLBW preterm infants. However, Enterococcus remains a key reservoir of resistance, and antibiotic exposure continues to drive HGT. “Pairing evidence-based probiotics with antibiotic stewardship and infection control can help protect this population,” researchers stated. Further research is needed to optimize probiotic dosing, duration, and strain selection to maximize benefits and minimize risks. For families and NICUs, a holistic approach aligning feeding practices, hygiene protocols, and antibiotic prescribing is essential. .
Journal reference: Kiu, R., Darby, E. M., Alcon-Giner, C., Acuna-Gonzalez, A., Camargo, A., Lamberte, L. E., Phillips, S., Sim, K., Shaw, A. G., Clarke, P., van Schaik, W., Kroll, J. S., & Hall, L. J. (2025). Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants. Nat Commun 16, 7569. DOI: 10.1038/s41467-025-62584-2, https://www.nature.com/articles/s41467-025-62584-2
