Researchers in the UK assessed the effects of probiotics and antibiotics on the gut microbiome in two groups of VLBW human-milk-fed preterm infants, where one group received probiotics and the other did not.
“Our findings underscore the complex interplay between antibiotics, probiotics and horizontal gene transfer (HGT) in shaping the neonatal microbiome and support further research into probiotics for antimicrobial stewardship in preterm populations,” they wrote.
Reducing risks for premature infants
According to the World Health Organization (WHO), over 10% of infants worldwide are born prematurely, classified as before 37 weeks gestation, and around 1.4% are born weighing under 1.5 kg (3.3 lb), categorizing them as VLBW infants.
These infants can have underdeveloped immune systems, putting them at risk of infections such as necrotising enterocolitis and sepsis, which are caused by antibiotic-resistant bacteria. Neonatal intensive care units therefore often must treat preterm infants with antibiotics, but this can disrupt their gut microbiota and can encourage the growth of antibiotic resistance genes, which can lead to longer hospital stays.
The WHO recommends probiotic supplementation for very preterm, human-milk-fed infants to support gut health, and approximately 40% of UK neonatal intensive care units now use probiotics, specifically Bifidobacterium and Lactobacillus.
Probiotic supplementation reduces antibiotic resistance
The researchers selected 92 stool samples from 34 VLBW infants involved in a previous cohort study, all of whom had been fed human milk. One group received probiotics (Bifidobacterium bifidum and Lactobacillus acidophilus, twice daily from birth until approximately 34 weeks). The other did not.
Stool samples were collected at weeks one, two and three of the infants’ lives for DNA extraction and sequencing to study the bacteria. The researchers used shotgun metagenomics to track the microbiome and resistome changes during the first three weeks of life, under both probiotic and antibiotic exposure. They also tested plasmid-mediated antibiotic resistance gene transfer in an infant gut model.
The results showed that the probiotic supplementation was effective in reducing the prevalence of antibiotic resistance genes in the gut microbiome and decreasing the load of multidrug-resistant pathogens. It also restored the typical microbiota profile seen in early life.
The probiotic supplementation was found to rapidly establish beneficial Bifidobacterium species through a specialized metabolism of human milk oligosaccharides (HMOs), which can support colonization resistance and deplete resources needed by competing pathogens, the researchers noted. This suppressed antibiotic resistance gene-rich pathobionts—the microorganisms that can exacerbate disease, and lowered the amount of antibiotic resistance genes.
The researchers noted that despite this protective effect, the probiotics could not fully block horizontal gene transfer, the movement of material between organisms other than from parent to offspring, as the transfer of resistance genes persisted even in Bifidobacterium-dominant communities.
“Our findings suggest that probiotic supplementation with B. bifidum and L. acidophilus not only supports beneficial microbial communities but also plays a role in reducing [multidrug-resistant] bacteria and overall [antibiotic resistant gene] carriage,” the researchers concluded.
They added that a longer sampling period would be beneficial to capture longer-term impacts of antibiotics and probiotics on microbiome development.
“Future studies involving larger sample sizes, extended sampling windows and multi-site designs could provide more comprehensive insights into the dynamic interactions between antibiotics, probiotics and the neonatal microbiome,” they wrote.
Source: Nature Communications. doi: 10.1038/s41467-025-62584-2. “Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants”. Authors: Kiu, R. et al.