Harnessing probiotics to reduce infections and AMR in preterm infants: expert commentary

Recent research shows that probiotics may help combat antimicrobial resistance in preterm infants. Senior study author Professor Lindsay J Hall explains how introducing these beneficial microbes into neonatal care as a low-cost, low-risk intervention can protect against life-threatening infections and reduce multidrug-resistant bacteria in the gut to improve infant health and support global antimicrobial stewardship.

Antimicrobial resistance (AMR) is one of the most urgent public health threats of our time. It already causes more than 1.2 million deaths annually, with projections suggesting this could rise to 10 million by 2050 without effective solutions in place.

The neonatal period is a particularly high-risk window: preterm babies, especially those with very low birth weight, have immature immune systems and are frequently exposed to broad-spectrum antibiotics in neonatal intensive care units (NICUs).

This combination creates a perfect storm, disrupting microbiome development, encouraging colonisation by opportunistic drug-resistant pathogens, and driving the spread of resistance. Novel strategies to protect infant health while reducing AMR risk are therefore urgently needed, and probiotics are emerging as a promising solution.

Our recent study, published in the journal Nature Communications and led by teams at the University of Birmingham, Quadram Institute Bioscience in Norwich, Imperial College London, and Norfolk and Norwich University Hospital, demonstrates that probiotic supplementation can reduce the burden of AMR and multidrug-resistant bacteria in the gut, while promoting a more typical early-life microbiome.

Building on findings from our larger BAMBI study in over 220 infants, the current study provides further evidence that probiotics may play a dual role in both protecting against infection and mitigating AMR by shifting the balance towards beneficial microbes while reducing the risks associated with resistant pathogens.

Why probiotics in preterm infants?

Preterm infants weighing less than 1500 g account for only 1-1.5% of global births, although rates can be considerably higher in some regional settings. Despite the relatively small numbers, these infants face disproportionately high risks of sepsis, necrotising enterocolitis (NEC), chronic morbidity and mortality.

Antibiotics are often essential for managing infection risk, yet they deplete beneficial commensals and encourage the dominance of opportunistic pathogens or pathobionts, such as Enterococcus and Klebsiella, many of which harbour multiple resistance genes.

Over the past decade, probiotics have been integrated into routine care in many NICUs, with compelling evidence that they reduce sepsis and NEC. However, their potential role in antimicrobial stewardship and reducing AMR remained less well understood.

Study design

We analysed 34 very-low-birth-weight infants cared for in UK NICUs – a subset from the BAMBI study. Infants received either antibiotics alone or antibiotics plus a probiotic formulation containing Bifidobacterium bifidum (B. bifidum) and Lactobacillus acidophilus (brand name Infloran). All infants received either expressed or donor human breast milk, ensuring a consistent nutritional context.

A total of 92 longitudinal stool samples collected over the first three weeks of life were subjected to deep shotgun metagenomic sequencing combined with bacterial isolation and whole-genome sequencing to characterise microbial composition and resistome profiles. Crucially, this approach also enabled the tracking of horizontal gene transfer – a major mechanism driving the spread of AMR – which we validated using an in vitro model colon system.

What did we find?

Probiotic colonisation and microbiome maturation

In infants receiving probiotics, B. bifidum rapidly colonised the gut and supported the establishment of a microbial community more closely resembling that of full-term infants. Beneficial commensals, including other Bifidobacterium species, were enriched, while levels of pathobionts were reduced. These findings are consistent with our previous work, which shows that Bifidobacterium can metabolise human milk oligosaccharides in breast milk, conferring a competitive ecological advantage.

Fewer AMR determinants

Probiotic-supplemented infants carried significantly fewer AMR genes (ARGs) in their gut microbiomes. In contrast, infants without probiotics harboured a broader spectrum of resistance determinants, including genes conferring resistance to aminoglycosides, β-lactams, macrolides and tetracyclines. Worryingly, this group also carried genes for resistance to last-resort antibiotics such as colistin.

Reduced multidrug-resistant pathogens

Infants given probiotics had a markedly lower abundance of multidrug-resistant organisms. Pathogens strongly linked with bloodstream infections and prolonged hospitalisation, such as resistant Enterococcus, Staphylococcus, Klebsiella and Escherichia coli, were significantly reduced.

Selective effects of probiotics

Importantly, probiotic supplementation did not indiscriminately disrupt the microbiome. Non-resistant strains, including commensal E. coli, were maintained or even promoted, suggesting probiotics selectively target resistant strains while supporting beneficial microbes. This ecological selectivity is a key strength, indicating probiotics can complement antibiotic therapy rather than undermine it.

Clinical relevance of probiotics

This study provides proof-of-principle that probiotics can act as a low-cost, low-risk supplementation in NICUs, not only preventing severe infections but also reducing the burden of AMR.

The absence of colistin resistance in supplemented infants is particularly notable, highlighting the ability of Bifidobacterium to create a gut environment less permissive to resistant pathogens.

These dual benefits align with recommendations by the World Health Organization for probiotic use in preterm infants and point to a role for probiotics in broader infection-control and antimicrobial stewardship strategies.

Study limitations and wider implications

While encouraging, the study sample size was small and focused on the first three weeks of life. Larger studies are required to confirm the durability and reproducibility of these effects, as well as to understand their impact on clinical outcomes, such as the incidence of sepsis and length of hospital stay.

The efficacy of probiotics is context-dependent, and the success and impact of colonisation vary with maternal factors, baseline microbiomes, antibiotic regimens and feeding practices. Future trials must therefore test probiotic strategies across multiple NICUs and ideally across diverse global settings. This is essential given the worldwide burden of preterm birth and the geographic variability in both microbiome development and AMR threats.

This work also highlights several key principles for the development of microbiome- and probiotic-based therapeutics.

First, probiotics demonstrate ecological selectivity, reducing ARGs, including those conferring resistance to last-resort antibiotics, while sparing beneficial commensals.

The benefits of probiotics are enhanced through nutrient–microbe synergy, as breast milk provides human milk oligosaccharides that create a metabolic niche supporting bifidobacterial dominance.

Probiotics can be integrated into antimicrobial stewardship efforts, complementing existing infection-prevention strategies and, in some contexts, even serving as alternatives to antibiotics for displacing multidrug-resistant bacteria.

Looking ahead, these insights could inform the development of precision probiotic or synbiotic formulations tailored to specific populations, particularly for vulnerable groups such as preterm infants.

Conclusions

Our findings provide evidence that probiotic supplementation in preterm infants can both promote healthier microbiome development and reduce the burden of multidrug-resistant bacteria.

While further work is needed to validate these results and assess long-term clinical outcomes, probiotics represent a promising, low-cost intervention with the potential to improve neonatal health and contribute to global antimicrobial stewardship efforts.

Take-home messages: preterm infants and probiotics

• Preterm infants given probiotics alongside antibiotics carried fewer multidrug-resistant bacteria and lower levels of ARGs
• Probiotics promoted colonisation with beneficial microbes, making the gut microbiome resemble that of term-born infants
• Resistance to last-resort antibiotics such as colistin was observed in non-supplemented infants but absent in those receiving probiotics
• While promising, the findings need confirmation in larger, multicentre and global studies, given the variability across NICU settings
• Probiotics may provide a dual-benefit intervention in NICUs by preventing infections and mitigating AMR, with major implications for neonatal health and global antimicrobial stewardship.

Author

Lindsay J Hall PhD
Chair of microbiome research, University of Birmingham and group leader, Quadram Institute Bioscience, UK