A small UK study of preterm infants is shedding new light on the impact of antibiotics and probiotics on the infant gut microbiome.
The study, published last week in Nature Communications, found that among a cohort of very low birth weight (VLBW) infants, those who received probiotic supplements had fewer antibiotic-resistance genes (ARGs) and multidrug-resistant (MDR) pathogens in their gut than those who didn’t, even when they also received antibiotics. The infants who received probiotics also had a higher abundance of beneficial bacteria.
The authors of the study say the findings highlight the role that probiotics could play in antimicrobial stewardship and infection control in vulnerable preterm infants.
“Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold,” lead study author Lindsay Hall, PhD, chair of microbiome research at the University of Birmingham, said in a university press release.
Antibiotic exposure common in preterm infants
For the study, Hall and colleagues from the University of Birmingham, Quadrum Institute Bioscience, and Imperial College London analyzed the gut microbiomes of 34 VLBW infants who were all exclusively fed human milk. The infants were split into two groups: the probiotics-supplemented (PS) cohort and the non–probiotic-supplemented (NPS) cohort.
The infants in the PS group received probiotics containing Bifodobacterium bifidum and Lactobacillus acidophilus, two species of beneficial bacteria commonly used in probiotics. Some infants in both cohorts also received empiric benzylpenicillin and gentamicin, while others had no antibiotic exposure.
Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold.
As the authors explain, roughly 40% of neonatal intensive care units (NICUs) in the United Kingdom provide probiotic supplementation to VLBW infants, who have underdeveloped immune systems and are routinely administered broad-spectrum antibiotics to ward off infections with drug-resistant pathogens. Probiotics are used to counter the effects of early antibiotic exposure, which can disrupt the normal development of the infant gut microbiome and has been associated with higher levels of ARGs in preterm infants.
“Importantly, probiotics have also been observed to reduce the abundance of ARGs in the gut microbiota of preterm infants, bringing it closer to levels seen in full-term infants,” the authors wrote.
Using shotgun metagenomic sequencing, the researchers analyzed infant fecal samples, assessing microbiome species and strain dynamics, along with the effects of probiotics and antibiotics, during the first 3 weeks of life. Shotgun metagenomic sequencing involves taking the DNA out of all the bacteria in the samples, breaking it into small pieces, and analyzing all of the pieces.
More beneficial bacteria, fewer ARGs in probiotic recipients
The analysis revealed that the gut microbiomes of the PS infants were notably different from those of the NPS infants, with the former dominated by Bifidobacterium and the latter dominated by pathobionts (species that under certain conditions can become pathogenic) such as Klebsiella pneumoniae, Escherichia coli, and Staphylococcus epidermis. Another potentially pathogenic species, Enterococcus faecalis, was prominent in the gut microbiota of both groups.
The abundance of ARGs was also significantly higher in NPS infants than PS infants across the first 3 weeks. And genomic analysis of ARGs found in potentially pathogenic species in each cohort indicated that those in the NPS infants more frequently exhibited MDR characteristics.
“The presence of these ARGs, underscores the potential for reduced antibiotic efficacy in this vulnerable population and highlights the need for careful and improved antibiotic stewardship in NICU settings,” Hall and colleagues wrote.
In addition, when the researchers compared ARG profiles in the antibiotic versus control groups within each cohort, they found that both the antibiotic-treated and control infants in the NPS group had higher ARG counts than their counterparts in the PS, a finding they say suggests a “potential ARG-suppressive effect of B. bifidum in the preterm gut.”
“We have already shown that probiotics are highly effective in protecting vulnerable preterm babies from serious infections, and this study now reveals that these probiotics also significantly reduce the presence of antibiotic resistance genes and multidrug-resistant bacteria in the infant gut,” said Hall.
The analysis also found, however, that while there were a greater number of plasmids—mobile pieces of DNA that carry ARGs and other resistance mechanisms—in the NPS infants compared with the PS cohort, even high levels of Bifidobacterium did not prevent the transfer of plasmids carrying ARGs between bacteria. The finding was revealed in an ex vivo experiment that simulated the neonatal gut environment and showed horizontal gene transfer (HGT) between strains of Enterococcus isolated from the infants.
That finding is significant because antibiotic exposure can create a selection pressure that favors ARG-carrying plasmids. So even if children who receive probiotics are carrying fewer ARGs, those ARGs could still proliferate in their gut if they’re exposed to antibiotics.
“This emphasises the need for further studies to evaluate the role of probiotics not only in microbial colonisation but also in their potential impact on HGT dynamics, particularly in environments where antibiotics are heavily used,” the authors wrote.