A randomized clinical trial found little effect of exclusive human milk diet on gut microbiota compared with a combined human and bovine milk diet among preterm infants. These findings were published in JAMA Network Open.

The study enrolled preterm infants born at fewer than 30 weeks’ gestation within the first 72 hours of life. The infants were given the intervention of 150 mL/kg human milk-derived fortifiers per day with pasteurized human milk (n=63) or the control condition of 150 mL/kg bovine-derived fortifier with bovine formula (n=63) in addition to mother’s supply until 34 weeks’ postmenstrual age. Alpha and beta diversity profiles in the gut microbiota were compared between human and bovine milk recipients.

Human and bovine milk recipients were born at a median gestational age of 27.14 (IQR, 25.7-28.1) and 27.0 (IQR, 26.0-28.1) weeks; they had birthweights of 930 (IQR, 733-1095) and 910 (IQR, 704-1054) g; 24% and 24% were multiple births; 60% and 51% were boys; 59% and 56% were delivered by cesarean section; and 90% and 88% received antenatal steroids, respectively.


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There were no significant group differences in any clinical characteristics regarding days of breast milk intake from their mothers, chronic lung disease rates, surgical necrotizing enterocolitis rates, days spent in the intensive care unit and high dependence days, and mortality.

Human and bovine milk recipients had similar changes in weight from birth to 34 weeks (mean difference range, -0.88 to -0.83 standard deviation score; P =.63) or birth to discharge (mean difference range, -0.94 to -0.81 standard deviation score; P =.48).

Over multiple time points, study site and use of probiotics associated with bacterial profiles at more than one time point.

Overall, milk source did not associate with bacterial richness (estimate, -0.951; P =.23) or Shannon diversity (estimate, -0.094; P =.06), but at study completion, both bacterial richness (P =.02) and Shannon diversity (P =.04) were related with milk group.

For individual microbiota components, days of life was negatively related with the abundance of Staphylococcus (estimate, -0.173; P <.001) and Corynebacterium (estimate, -0.006; P =.01) and positively related with Enterobacter (estimate, 0.125; P <.001), Veillonella (estimate, 0.034; P <.001), Clostridium (estimate, 0.0184; P <.001), Escherichia (estimate, 0.050; P <.001), and Bifidobacterium (estimate, 0.042; P <.001). The abundance of Bifidobacterium depended on use of probiotics (P <.001), days of antibiotic use (P =.02), and days mother’s milk received (P =.01).

Stratified by milk group, the only significant difference was the relative abundance of Lactobacillus, which was lower in the human milk group than the combined human and bovine milk cohort (estimate, 0.056; P =.03).

This study may have been limited, as the protocol was modified due to the high rate of nonsurvival and unanticipated hospital transfer.

“These findings suggest that human milk products given to preterm infants to supplement a shortfall in mother’s own milk does not affect clinical outcomes via microbial mechanisms,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Embleton ND, Sproat T, Uthaya S, et al. Effect of an exclusive human milk diet on the gut microbiome in preterm infants: a randomized clinical trial. JAMA Netw Open. 2023;6(3):e231165. doi:10.1001/jamanetworkopen.2023.1165

This article originally appeared on Gastroenterology Advisor