Probiotics Show Promise in Reducing Antibiotic Resistance in Vulnerable Preterm Infants
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New research indicates that targeted probiotic supplementation-specifically strains of Bifidobacterium and Lactobacillus-could significantly improve gut health and combat the rise of antibiotic resistance in very-low-birth-weight (VLBW) preterm infants. These infants, often requiring prolonged stays in neonatal intensive care units (NICUs), are particularly susceptible to disruptions in early microbial colonization and the subsequent expansion of antibiotic-resistant genes (ARGs).
The findings, published in Nature Communications, offer a strategic approach to antimicrobial stewardship and newborn care, potentially lessening the burden of multidrug-resistant (MDR) organisms in a highly vulnerable population.
Study details and Key Findings
Researchers enrolled 34 VLBW infants exclusively fed human milk. The study compared infants receiving a probiotic supplement (PS) containing Bifidobacterium bifidum and Lactobacillus acidophilus to a control group that did not (NPS). Using shotgun metagenomic sequencing, the team analyzed the infants’ gut microbiome and resistome during the first three weeks of life.They also conducted plasmid-transfer experiments in a neonatal gut model to assess the potential for horizontal gene transfer (HGT).
The PS group exhibited fewer ARGs and reduced growth of common pathobionts, including Enterococcus, Escherichia, and Klebsiella, compared to the NPS group. Beneficial Bifidobacterium species, such as B. breve and B. longum subsp. infantis, were more prevalent in the probiotic-supplemented infants. Furthermore, Escherichia and Klebsiella strains in the PS group were less likely to display MDR traits observed in the NPS group.
Interestingly, brief, standardized antibiotic use did not significantly alter overall microbiome diversity in either group. This suggests that the observed changes were primarily driven by the probiotic supplementation, rather than antibiotic exposure.
Did You Know? The human gut microbiome contains trillions of microorganisms,playing a critical role in health,immunity,and even brain function. Disruptions to this delicate ecosystem, especially in early life, can have lasting consequences.
Horizontal Gene Transfer and Probiotic Limitations
Mechanistic studies revealed both the promise and limitations of this approach.In an ex vivo infant gut model, a 137-kb megaplasmid carrying the aminoglycoside resistance gene aac6-aph2 transferred between Enterococcus strains, conferring gentamicin resistance even in a Bifidobacterium-rich environment. This highlights that while probiotics can reduce ARG burden and impede MDR colonization, HGT remains a possibility within early-life microbial communities.
Clinical Implications and Guidelines
These findings align with expert recommendations supporting probiotic use in select preterm infant populations to reduce the risk of necrotizing enterocolitis (NEC) and mortality. Though, emphasis is placed on the importance of high-quality, safe products and strain specificity. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommends using rigorously manufactured products with documented strains and viable counts, alongside standardized NICU protocols for product selection, storage, and administration 1.
| Factor | Probiotic Supplement (PS) Group | No Probiotic Supplement (NPS) Group |
|---|---|---|
| Antibiotic Resistance Genes (ARGs) | fewer | More |
| Pathobiont Growth | Reduced (Enterococcus, Escherichia, Klebsiella) | Increased |
| Bifidobacterium Species | Higher prevalence (B. breve, B. longum subsp. infantis) | Lower prevalence |
| MDR Traits in Escherichia/Klebsiella | Less frequent | More frequent |
Pharmacist’s Viewpoint
NICU pharmacists can play a pivotal role in implementing probiotic strategies as a core component of antimicrobial stewardship. This includes rigorous product vetting-assessing strain type, colony-forming unit (CFU) content, excipients, and manufacturing quality-as well as establishing protocols for storage, handling, and timing to maximize benefits and minimize antimicrobial inactivation. Collaboration with neonatology and infection prevention teams is crucial for integrating probiotics into broader stewardship pathways aimed at suppressing ARG emergence and MDR colonization.
Pro Tip: Pharmacists should educate clinicians and families about the realistic expectations of probiotic supplementation. While probiotics can reduce ARG prevalence and control growth, they cannot entirely eliminate the risk of plasmid-mediated resistance spread. Success depends on using the correct strains, dosages, and protocols.
What are the biggest challenges to widespread probiotic adoption in NICUs, and how can these be overcome? how can long-term monitoring of gut microbiome composition inform probiotic strategies for preterm infants?
Conclusion
Early probiotic supplementation in VLBW preterm infants resulted in fewer ARGs, reduced MDR from key pathobionts, and increased levels of beneficial Bifidobacterium during a critical period of advancement. While HGT remains a concern,these results support a well-defined probiotic plan-led by pharmacists-as an integral part of NICU care and antimicrobial control. Further research and long-term follow-up are needed to clarify durability, safety, and clinical outcomes 2.
REFERENCES
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Probiotics for preterm babies lowered antibiotic resistant bacteria in gut, new study shows. EurekAlert! Published August 15, 2025. Accessed August 19, 2025. https://www.eurekalert.org/news-releases/1094868
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Kiu, R., Darby, E.M., Alcon-Giner, C. et al. impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants. Nat Commun 16, 7569 (2025).https://doi.org/10.1038/s41467-025-62584-2
The increasing prevalence of antibiotic resistance is a global health crisis,driving the need for innovative strategies to preserve antibiotic effectiveness. Microbiome-directed therapies, such as probiotic supplementation, represent a promising avenue for addressing this challenge, particularly in vulnerable populations like preterm infants.Ongoing research is focused on identifying optimal probiotic strains, dosages, and delivery methods to maximize benefits and minimize risks. The long-term impact of early-life microbiome modulation on immune development and overall health remains an active area of investigation.
Frequently Asked Questions About Probiotics and Preterm Infants
- What are probiotics, and how do they work? Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. They work by modulating the gut microbiome,competing with harmful bacteria,and enhancing immune function.
- Are all probiotics the same? no. different probiotic strains have different effects. The choice of strain is crucial for achieving specific health outcomes.
- What is the role of the gut microbiome in preterm infants? The gut microbiome plays a vital role in nutrient absorption,immune system development,and protection against pathogens.Preterm infants have an underdeveloped microbiome, making them more susceptible to infections and complications.
- Can probiotics prevent necrotizing enterocolitis (NEC)? Probiotic supplementation has been shown to reduce the risk of NEC, a serious intestinal disease, in some preterm infants.
- Are there any risks associated with probiotic use in preterm infants? while generally safe, probiotics can cause mild side effects like gas or bloating. in rare cases, more serious complications have been reported, particularly in very sick infants.
We hope this article provided valuable insights into the potential of probiotics in improving the health of vulnerable preterm infants. Please share this information with your network, leave a comment below with your thoughts, or subscribe to our newsletter for more updates on cutting-edge medical research.
