OBJECTIVE: Articles previously published by Sullivan et al. and Cristofalo et al. were reanalyzed using the proportion of cow milk-based nutrition received to determine whether that affected clinical outcomes during hospitalization for infants birth weight 500-1250 g. Abrams et al. showed in the same cohort incidences of necrotizing enterocolitis (NEC), NEC requiring surgery and sepsis increased proportionally to the amount of dietary cow milk. METHODS: The data from the two studies conducted under essentially the same protocol were combined yielding a cohort of 260 infants receiving a diet ranging from 0% to 100% cow milk. Data analysis utilized negative binomial regression which mitigates differences between subjects in terms of their time on study by incorporating that number into the statistical model. The percent of cow milk-based nutrition was the only predictor investigated. RESULTS: For all outcomes the larger the amount of cows milk in the diet the greater the number of days of that intervention required. A trend toward statistical significance was seen for ventilator days; however, only parenteral nutrition (PN) days and days to full feeds achieved statistical significance. CONCLUSIONS: Incorporation of any cow milk-based nutrition into the diet of extremely premature infants correlates with more days on PN and a longer time to achieve full feeds. There was a nonstatistically significant trend toward increased ventilator days. These represent additional clinical consequences of the use of any cow milk-based protein in feeding EP infants.

Human milk contains over 200 distinct oligosaccharides, which are critical to shaping the developing neonatal gut microbiome. To investigate whether a complex mixture of human milk oligosaccharides (HMOs) would similarly modulate the adult gut microbiome, HMO-Concentrate derived from pooled donor breast milk was administered orally to 32 healthy adults for 7 days followed by 21 days of monitoring. Fecal samples were collected for 16S rRNA gene sequencing, shotgun metagenomics, and metabolomics analyses. HMO-Concentrate induced dose-dependent Bifidobacterium expansion, reduced microbial diversity, and altered microbial gene content. Following HMO cessation, a microbial succession occurred with diverse taxonomic changes-including Bacteroides expansion-that persisted through day 28. This was associated with altered microbial gene content, shifts in serum metabolite levels, and increased circulating TGFβ and IL-10. Incubation of cultured adult microbiota with HMO-Concentrate induced dose-dependent compositional shifts that were not recapitulated by individual HMOs or defined mixtures of the 10 most abundant HMOs in HMO-Concentrate at their measured concentrations. These findings support that pooled donor HMOs can exert direct effects on adult gut microbiota and that complex mixtures including low abundance HMOs present in donor milk may be required for maximum effect.Registration: ClinicalTrials.gov NCT05516225.