Mother’s own milk, hailed as nature’s perfect biofluid for newborns, is a dynamic, living system tailored intricately to meet the nutritional and immunological needs of the infant. Underscoring the complexity, this milk contains an array of bioactive components such as live immune cells, hormones, growth factors, enzymes, and an evolving microbiome that adapts over time. In contrast, pasteurized donor milk, typically sourced from healthy lactating women and subjected to Holder pasteurization, loses many of these delicate constituents, raising concerns about its ability to fully replicate the protective and developmental benefits of a mother’s own milk.

Holder pasteurization—a heat treatment involving warming donor milk to 62.5°C for 30 minutes—effectively inactivates pathogenic microorganisms, ensuring safety for vulnerable preterm infants. Yet, this process also denatures vital proteins like lactoferrin and immunoglobulins, diminishes enzyme activity such as bile salt-stimulated lipase, and disrupts beneficial microbes and microbiota-derived metabolites. The review emphasizes that such alterations may influence gut microbial colonization and maturation, a critical determinant of gut barrier function and immune development in preterm neonates.

Preterm infants inherently face a precarious intestinal environment characterized by immaturity, increased permeability, and susceptibility to necrotizing enterocolitis (NEC), a devastating inflammatory condition of the bowel. The authors highlight that mother’s own milk robustly supports gut integrity through bioactive components that promote epithelial growth, modulate inflammation, and foster beneficial microbial symbiosis. In contrast, donor milk’s diminished bioactivity may attenuate these protective mechanisms, potentially impacting intestinal barrier maturation and the infant’s immune resilience against NEC and sepsis.

The review delves into the role of human milk oligosaccharides (HMOs), complex sugars abundantly present in mother’s milk but variably altered by pasteurization. HMOs serve as prebiotics shaping neonatal gut microbiota by encouraging colonization by Bifidobacteria and other commensal microbes. These microbial populations coordinate immune signaling and metabolic functions vital for intestinal homeostasis. The extent to which pasteurization compromises HMO integrity or their functional capacity remains an area demanding deeper exploration, flagged by Sundararajan and Ma as crucial for refining donor milk processing techniques.

Beyond microbial and immunological aspects, the hormonal and growth factor milieu is dramatically different. Mother’s milk delivers epidermal growth factor (EGF), transforming growth factor-beta (TGF-β), and insulin-like growth factors (IGFs) that stimulate enterocyte proliferation and modulate immune tolerance. Pasteurized donor milk often shows reduced concentrations of these bioactive molecules, potentially influencing the timing and quality of intestinal maturation in premature infants. These changes underscore a biological “gap” between milk types that transcends mere nutrient content into sophisticated developmental programming.

The authors advocate for innovative intervention strategies aimed both at enhancing donor milk quality and supplementing bioactive deficits. This might involve alternative pasteurization methods like high-pressure processing, ultraviolet irradiation, or flash-heat treatments that better preserve milk’s functional components without compromising safety. Moreover, supplementation with purified bioactives, probiotics, or prebiotics represents a promising frontier to ameliorate the biological gap, supporting a more physiological intestinal environment in preterm neonates.

Given the vulnerable state of preterm infants whose gut microbiome is continually evolving, the review further details how pasteurized donor milk’s impact on microbial diversity and metabolic capacity could affect systemic immune training. Studies referenced demonstrate that donor milk-fed infants often showcase delayed colonization by beneficial bacteria and altered metabolomic profiles, correlating with increased inflammation and potentially impaired neurodevelopmental trajectories later in life. These findings emphasize a pressing need to reconsider donor milk processing and neonatal nutrition protocols in NICUs globally.

Interestingly, Sundararajan and Ma also point to growing evidence of epigenetic influences mediated by human milk components. Epigenetic programming during this critical window shapes gene expression patterns, influencing immunity, metabolism, and disease susceptibility in adulthood. The biological gap between mother’s own milk and pasteurized donor milk may thus extend to epigenomic consequences, an insight that opens new research avenues on long-term infant health beyond neonatal survival rates.

Ethical and practical considerations surrounding milk banking and the equitable distribution of high-quality human milk products are underscored in the review. The authors call for multidisciplinary collaboration among neonatologists, biochemists, nutritionists, and policymakers to develop standards that minimize biological disparities, enhance milk safety, and consider the individualized needs of preterm infants. This systemic approach could revolutionize clinical practice and milk banking paradigms worldwide.

Moreover, this review reinforces an urgent call to elevate maternal lactation support and optimize collection methods to increase the availability of mother’s own milk in NICUs. Enhanced maternal nutrition, lactation counseling, and early milk expression techniques may reduce dependency on donor milk, ensuring more infants receive the tailored benefits of their own mother’s biological fluid. Supporting the mother-infant dyad remains a cornerstone of promoting intestinal health and promoting lifelong well-being in this fragile population.

In conclusion, the work of Sundararajan and Ma provides a compelling, multidimensional exploration of the biological chasm between mother’s own milk and pasteurized donor milk and its profound implications for intestinal health in preterm infants. As scientific innovation progresses, bridging this gap will be paramount to advancing neonatal care, mitigating complications, and fostering optimal development during the earliest, most vulnerable stage of life. The future of neonatal nutrition hinges on marrying safety with biological fidelity—ensuring that the life-giving properties of human milk are preserved in every drop fed to preterm infants.

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Article References:

Sundararajan, S., Ma, B. Review of the biological gap between mother’s own milk and pasteurized donor milk: implications for intestinal health in preterm infants. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-05025-0

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DOI: https://doi.org/10.1038/s41390-026-05025-0