Formula feeding is associated with a 70% increase in antibiotic resistance gene (ARG) abundance in the gut microbiome of infants compared with breast milk, US and Finnish researchers have reported in the American Journal of Clinical Nutrition.
To determine the impact of early exposure to infant formula on the ARG load in newborns and infants born either pre- or full-term, the researchers cross-sectionally sampled the gut metagenomes of 46 infants born prematurely to build a generalised linear model and collected extensive data on the babies’ diet during the first month of life.
They then cross-validated the model using 242 infant gut metagenomes from public databases. Their hypothesis was that diet causes a selective pressure that influences the microbial community of the infant gut and that formula might carry an abundance of bacterial species that carry ARGs.
The researchers found that formula-feeding increases the ARG load compared with an exclusively human milk diet. The relative abundance of ARGs carried by gut bacteria was 69% higher in infants receiving formula (fold change, 1.69; 95% confidence interval [CI], 1.12 to 2.55) compared with those who received human milk only. Several ARGs in formula-fed infants were enriched, including extended-spectrum beta-lactamase (ESBL) genes and genes encoding resistance to methicillin and erythromycin in Staphylococcus aureus.
Formula-fed infants also had a higher relative abundance of opportunistic pathogens, including S aureus, Staphylococcus epidermis, Klebsiella pneumoniae, Klebsiella oxytoca, and Clostridioides difficile, and significantly less bacterial species typically found in the gut, such as bifidobacteriaceae.
The study authors note that they did not follow up on the infants to determine whether those who were fed formula or had higher ARG abundance had more infections caused by antibiotic-resistant bacteria and that they could not confirm whether the ARGs were functional. But they say the findings suggest that the changes in formula-fed infants’ intestinal environment may result in more ARG-carrying bacteria.
“Infants born prematurely are at particular risk of acquiring severe and life-threatening infections,” they wrote. “Thus, increased ARG loads in formula-fed infants and the enrichment of potentially pathogenic bacteria are concerning.”
Study details
Early-life formula feeding is associated with infant gut microbiota alterations and an increased antibiotic resistance load
Katariina M M Pärnänen, Jenni Hultman, Melina Markkanen, Reetta Satokari, Samuli Rautava, Regina Lamendella, Justin Wright, Christopher J McLimans, Shannon L Kelleher, Marko P Virta
Published in the American Journal of Clinical Nutrition on 22 October 2021
Abstract
Background
Infants are at a high risk of acquiring fatal infections, and their treatment relies on functioning antibiotics. Antibiotic resistance genes (ARGs) are present in high numbers in antibiotic-naive infants’ gut microbiomes, and infant mortality caused by resistant infections is high. The role of antibiotics in shaping the infant resistome has been studied, but there is limited knowledge on other factors which affect the antibiotic resistance burden of the infant gut.
Objectives
Our objectives were to determine the impact of early exposure to formula on the ARG load in neonates and infants born either pre- or full-term. Our hypotheses were that diet causes a selective pressure that influences the microbial community of the infant gut, and formula exposure would increase the abundance of taxa that carry ARGs.
Design
Cross-sectionally sampled gut metagenomes of 46 neonates were used to build a generalized linear model to determine the impact of diet on ARG loads in neonates. The model was cross-validated using neonate metagenomes gathered from public databases using our custom statistical pipeline for cross-validation.
Results
Formula-fed neonates had higher relative abundances of opportunistic pathogens such as Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Klebsiella oxytoca, and Clostridioides difficile. The relative abundance of ARGs carried by gut bacteria was 69% higher in the formula receiving group (fold change 1.69, (95% CI 1.12, 2.55), P = 0.013, n = 180) compared to ex
Conclusions
The novel finding that formula exposure is correlated with a higher neonatal ARG burden lays the foundation that clinicians should consider feeding mode in addition to antibiotic use during the first months of life to minimize the proliferation of antibiotic-resistant gut bacteria in infants.
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