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Page 2 of 18 Chen et al. Microbiome Res Rep 2025;4:8 https://dx.doi.org/10.20517/mrr.2024.44

Methods: A comprehensive search was conducted across MEDLINE, Embase, and Cochrane databases. Eight out
of the 717 publications identified were included. Data on gut microbiota composition, alpha diversity, and
taxonomic differences between DHM- and MOM-fed preterm infants were extracted and analyzed.

Results: The microbiome composition was distinct between the two feeding groups. Alpha diversity measures
were lower in DHM-fed infants, particularly when preterm formula (PF) was also provided. DHM-fed infants
showed higher abundances of Staphylococcaceae and Clostridiaceae, and lower abundances of Bacteroidetes and
Bifidobacterium.

Conclusion: The observed gut microbiome differences in DHM-fed preterm infants have previously been linked to
adverse health outcomes. This underlines the importance of increasing the awareness of MOM intake in preterm
infants. Further studies should explore the mechanisms through which human milk affects health outcomes.

Keywords: Fecal microbiome, premature neonate, milk bank, donor milk, breastmilk, human milk
oligosaccharides, secretory immunoglobulins, and the milk microbiota, influence the development of the

INTRODUCTION
Infants born very preterm (i.e., < 32 weeks of gestation) constitute a vulnerable population, characterized by
a significant risk of mortality and short- and long-term morbidities . Enteral feeding strategies are
[1]
[2]
suggested to reduce those risks . Enteral feeding with mother’s own milk (MOM) improves short- and
long-term health outcomes compared to preterm formula (PF). This includes lower rates of necrotizing
[3-7]
enterocolitis (NEC) and sepsis, and better neurodevelopmental outcomes .

[8]
In the very preterm population, achieving an exclusive MOM diet is not always feasible . Historically, when
sufficient MOM was unavailable, very preterm infants received PF. In recent years, with the establishment
of more donor human milk (DHM) banks, DHM is recommended as the second-best option by
organizations such as the World Health Organization and the European Society for Paediatric
Gastroenterology, Hepatology and Nutrition [5,9-13] . Albeit probably not to the same extent as MOM, DHM
also leads to fewer adverse neonatal outcomes, such as NEC, as compared to PF [7,14] . Research comparing
neonatal health outcomes between predominantly MOM or DHM diets is scarce and the available results
are inconsistent [7,15-17] . Some studies indicate that the incidence of NEC and other morbidities may be
dependent on the quantity of MOM provided to the infants, indicating that higher MOM exposition confers
[18]
greater benefits to the very preterm infant compared to DHM .
A potential mechanism through which human milk exerts its beneficial effects is via the composition and
function of the gut microbiome [19,20] . Bioactive factors in MOM, such as lactoferrin, human milk

preterm gut microbiota . However, it is essential to recognize that some of these bioactive factors are
[21]
affected by processing methods, including Holder pasteurization and multiple freeze-thaw cycles, to provide
preterm recipients with a safe product of DHM. In addition, biological factors such as the lactation stage
and characteristics of the donating mother may also influence the quality of the donated milk .
[22]
Subsequently, differences in composition between MOM and DHM may result in a difference in gut
microbial colonization of preterm infants.

Currently, only a limited number of studies have compared the effect of DHM vs. MOM on the gut
microbiota composition in preterm infants, hampering drawing a firm conclusion. This is important
however, as clear associations between early-life gut microbiota composition and short- and long-term
adverse outcomes, including NEC, sepsis, or neurodevelopmental impairment, have previously been
described [23-25] .