Preterm infants’ underdeveloped gastrointestinal and immune systems increase their risk of life-threatening complications like necrotizing enterocolitis (NEC). Donor human milk (DHM), rich in immunoglobulins and growth factors, reduces infection susceptibility, promotes intestinal maturation, and improves neurodevelopmental and metabolic outcomes. However, the effects of DHM and preterm formula on the fecal metabolome of these infants remain understudied. To elucidate the differential impacts of DHM versus preterm formula (PTF) on fecal metabolites in preterm infants, we conducted an untargeted metabolomics analysis within a randomized trial. Eligible preterm infants were divided into a DHM group (n = 12) and a PTF group (n = 12). All were fed according to the hospital’s protocol, beginning with minimal enteral nutrition within 24 h after birth. Feed volume was increased by 10–20 mL/(kg·d) until reaching full enteral feeding at 150 mL/(kg·d) every 3 h. Feces were collected 72 h after feeding initiation to analyze intestinal metabolism, and adverse reactions (abdominal distension, vomiting, gastric retention, diarrhea) were recorded. There were no statistically significant differences between the two groups in terms of delivery method, whether twins or multiple births, gender, gestational age at birth, birth weight, Apgar score, postnatal blood glucose, postnatal body temperature, time to start feeding, and time to first meconium passage (P > 0.05). The observed changes between the two groups were potentially associated with starch and sucrose metabolism, pyrimidine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, steroid hormone biosynthesis, nucleotide metabolism, arginine and proline metabolism, and galactose metabolism. The consumption of DHM was associated with alterations in metabolite profiles, suggesting a potential modulation of glycerophospholipid and amino acid metabolism compared with PTF. It has also been registered in the Chinese Clinical Trial Registry (ChiCTR), with the registration number of ChiCTR2500105584, retrospectively registered on July 7th, 2025.
Yang et al. (Mon,) studied this question.