Diet of Mother’s Milk Versus Formula Has No Effect on Preterm Infant Microbiome

There were no significant differences in the microbiomes of preterm infants who received a diet of only human milk compared to a diet of human milk plus bovine milk formula or fortifiers, according to an original investigation published in JAMA Network Open.

Investigators from the United Kingdom conducted a randomized clinical trial across 4 neonatal intensive care units in order to determine the effect of a diet of only human milk on gut bacterial richness, diversity, and proportions in preterm infants to 34 weeks postmenstrual age. The 126 preterm infants were recruited before 72 hours of age—only if they had received only mother’s own breast milk (MOM)—between 2017 and 2020, the study authors said.

Despite MOM being associated with lower rates of neonatal morbidities in preterm infants, many experience a shortfall of MOM, necessitating the use of bovine formula or pasteurized human milk from donor milk banks or commercial suppliers. Only a small number of randomized control studies on this topic exist, the study authors noted.

After obtaining parental consent, the infants were randomized to either a standard diet (MOM plus any formula to make up for MOM shortfall) or an exclusive human milk diet (the intervention group). The study authors noted that twins were randomized independently.

There were 63 infants randomized into the control group and 63 randomized into the intervention group, but there were no significant group differences in prespecified clinical outcomes, the study authors said. There were 12 infants who died, but the study authors said none of those deaths were attributed to necrotizing enterocolitis.

Daily stool samples were collected at baseline (the first sample after study enrollment), as well as at day of life 10, full feeds, days of life 21-28, and a final sample collected before stopping the dietary intervention at 34 weeks postmenstrual age. A total of 526 stool samples were collected from 119 infants.

Of all the factors that had the strongest association with the development of the gut microbiome through each time point, the study authors found that the use of probiotics were the only covariates that had a statistically significant association with the bacterial profiles at more than one time point.

“We found that trial group had no overall effect on gut microbiome richness or Shannon diversity, although infants randomized to exclusive human milk had different unweighted microbiome profiles, but not in weighted analysis,” the study authors said.

These findings suggested that the MOM-only diet had a greater effect on the low abundance of taxa, and are consistent with the finding that Lactobacillus was lower in infants who received only MOM. Lactobacillus has previously shown to be increased in breast-fed infants, the study authors noted, but it is unclear if this is an effect of a direct transfer or metabolism of breast milk.

“There were no effects on overall measures of gut bacterial diversity but there were effects on specific bacterial taxa previously associated with human milk receipt,” the study authors concluded. “These findings suggest that the clinical impact of human milk-derived products is not modulated via microbiomic mechanisms.”