PROTECTIVE ROLE OF HUMAN BREAST MILK AGAINST NECROTIZING ENTEROCOLITIS IN PRETERM INFANTS
Abstract
Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease that predominantly affects preterm infants, with high rates of morbidity and mortality. Human breast milk (HBM) has long been recognized as the most effective nutritional intervention for preventing NEC due to its unique bioactive components such as immunoglobulins, lactoferrin, glutamine, vitamins, and human milk oligosaccharides (HMOs), which act through mechanisms including strengthening the intestinal barrier, modulating immune responses, and regulating the gut microbiota. This narrative review aims to synthesize recent evidence on the protective role of HBM against NEC, with particular emphasis on the function of HMOs, probiotics, and complementary nutritional interventions designed to replicate or enhance HBM’s bioactivity. The methods applied in this review followed a narrative literature search in PubMed, Scopus, and Google Scholar for studies published between 2015 and 2025 on the effects of breastfeeding on NEC risk in preterm infants, using predefined eligibility criteria. The findings indicate that HBM significantly reduces NEC incidence, while supplemental interventions such as prebiotics and probiotics may serve as complementary strategies, particularly when the availability of mother’s own milk is limited. Overall, HBM remains the primary protective factor against NEC, and optimizing its provision in neonatal care is critical for improving outcomes among preterm infants.
References
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Dombrowska-Pali, A., Wiktorczyk-Kapischke, N., Chrustek, A., Olszewska-Słonina, D., Gospodarek-Komkowska, E., & Socha, M. W. (2024). Human Milk Microbiome—A Review of Scientific Reports. Nutrients, 16(10), 1420. https://doi.org/10.3390/nu16101420
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Gates, A., Marin, T., Leo, G. De, & Stansfield, B. K. (2021). Review of Preterm Human‐Milk Nutrient Composition. Nutrition in Clinical Practice, 36(6), 1163–1172. https://doi.org/10.1002/ncp.10570
Handoyo. (2018). Necrotizing Enterocolitis pada Neonatus Prematur dan Suplementasi Probiotik. Cermin Dunia Kedokteran, 45(5), 391–394. https://doi.org/10.55175/cdk.v45i5.795
Hassinger, D., Clausen, D. M., Nitka, S., Herdt, A., & Griffin, I. (2020). Analysis of Disialyllacto-N-Tetraose (DSLNT) Content in Milk From Mothers of Preterm Infants. Journal of Human Lactation, 36(2), 291–298. https://doi.org/10.1177/0890334420904041
Iftinan, Y., Ranti Filarma Negara Purnama, Lale Srigading Udayanti, Izza Ahmad Muharis, Jannatul Cahya Admiyanti, & Yusra Pintaningrum. (2023). Enterokolitis Nekrotik: Patofisiologi, Diagnosis dan Tatalaksana. Lombok Medical Journal, 2(1), 1–4. https://doi.org/10.29303/lmj.v2i1.2390
Kaban, R. K., Rohsiswatmo, R., Kautsar, A., Sutrisno, A. A., Hikmahrachim, H. G., & Hardiyanti, N. (2022). Risk factors of necrotizing enterocolitis-related mortality and patient survival: a preliminary prospective study. Paediatrica Indonesiana(Paediatrica Indonesiana), 62(3), 175–180. https://doi.org/10.14238/pi62.3.2022.175-80
Kanuri, S. H., Bagang, N., Ulucay, A. S., & Singh, G. P. (2023). Is Intestinal Cell Death in Necrotising Enterocolitis Assorted and Multifarious? A Special Focus on Risk Factors and Their Pathogenic Mechanisms. EMJ Gastroenterology. https://doi.org/10.33590/emjgastroenterol/10303125
Luthfi Taufik, M., & Lestari, D. (2021). Diagnosis dan Tatalaksana Enterokolitis Nekrotikans. Cermin Dunia Kedokteran, 48(4), 225. https://doi.org/10.55175/cdk.v48i4.1366
Martinez, R. C. R., Bedani, R., & Saad, S. M. I. (2015). Scientific evidence for health effects attributed to the consumption of probiotics and prebiotics: an update for current perspectives and future challenges. British Journal of Nutrition, 114(12), 1993–2015. https://doi.org/10.1017/S0007114515003864
Masi, A. C., Beck, L. C., Perry, J. D., Granger, C. L., Hiorns, A., Young, G. R., Bode, L., Embleton, N. D., Berrington, J. E., & Stewart, C. J. (2024). Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis. Cell Reports Medicine, 5(9), 101708. https://doi.org/10.1016/j.xcrm.2024.101708
Masi, A. C., Embleton, N. D., Lamb, C. A., Young, G., Granger, C. L., Najera, J., Smith, D. P., Hoffman, K. L., Petrosino, J. F., Bode, L., Berrington, J. E., & Stewart, C. J. (2021). Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis. Gut, 70(12), 2273–2282. https://doi.org/10.1136/gutjnl-2020-322771
Niño, D. F., Sodhi, C. P., & Hackam, D. J. (2016). Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nature Reviews Gastroenterology & Hepatology, 13(10), 590–600. https://doi.org/10.1038/nrgastro.2016.119
O’Rourke, L., Clarke, G., Nolan, A., Watkins, C., Dinan, T. G., Stanton, C., Ross, R. P., & Ryan, C. A. (2018). Tryptophan metabolic profile in term and preterm breast milk: implications for health. Journal of Nutritional Science, 7, e13. https://doi.org/10.1017/jns.2017.69
Paré, G., & Kitsiou, S. (2017). Handbook of eHealth Evaluation: An Evidence-Based Approach (F. Lau & C. Kuziemsky, Eds.). University of Victoria.
Parker, L. A., Koernere, R., Fordham, K., Bubshait, H., Eugene, A., Gefre, A., & Bendixen, M. (2024). Mother’s Own Milk Versus Donor Human Milk. Critical Care Nursing Clinics of North America, 36(1), 119–133. https://doi.org/10.1016/j.cnc.2023.09.002
Poulimeneas, D., Bathrellou, E., Antonogeorgos, G., Mamalaki, E., Kouvari, M., Kuligowski, J., Gormaz, M., Panagiotakos, D. B., & Yannakoulia, M. (2021). Feeding the preterm infant: an overview of the evidence. International Journal of Food Sciences and Nutrition, 72(1), 4–13. https://doi.org/10.1080/09637486.2020.1754352
Sajankila, N., Wala, S. J., Ragan, M. V., Volpe, S. G., Dumbauld, Z., Purayil, N., Mihi, B., & Besner, G. E. (2023). Current and future methods of probiotic therapy for necrotizing enterocolitis. Frontiers in Pediatrics, 11. https://doi.org/10.3389/fped.2023.1120459
Sami, A. S., Frazer, L. C., Miller, C. M., Singh, D. K., Clodfelter, L. G., Orgel, K. A., & Good, M. (2023). The role of human milk nutrients in preventing necrotizing enterocolitis. Frontiers in Pediatrics, 11. https://doi.org/10.3389/fped.2023.1188050
Savarino, G., Carta, M., Cimador, M., Corsello, A., Giuffrè, M., Schierz, I. A. M., Serra, G., & Corsello, G. (2021). Necrotizing enterocolitis in the preterm: newborns medical and nutritional Management in a Single-Center Study. Italian Journal of Pediatrics, 47(1), 226. https://doi.org/10.1186/s13052-021-01180-8
Sharif, S., Oddie, S. J., Heath, P. T., & McGuire, W. (2023). Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. The Cochrane Database of Systematic Reviews, 6(6), CD015133. https://doi.org/10.1002/14651858.CD015133.pub2
Shaw, A. G., Sim, K., Rose, G., Wooldridge, D. J., Li, M.-S., Misra, R. V., Gharbia, S., & Kroll, J. S. (2021). Premature neonatal gut microbial community patterns supporting an epithelial TLR-mediated pathway for necrotizing enterocolitis. BMC Microbiology, 21(1), 225. https://doi.org/10.1186/s12866-021-02285-0
Shulhan, J., Dicken, B., Hartling, L., & Larsen, B. M. (2017). Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products. Advances in Nutrition, 8(1), 80–91. https://doi.org/10.3945/an.116.013193
Syahniar, R., & Suri, A. A. (2020). Profil Mikrobiota ASI dan Perannya terhadap Saluran Cerna Bayi. Muhammadiyah Journal of Nutrition and Food Science (MJNF), 1(1), 8. https://doi.org/10.24853/mjnf.1.1.8-17
Wijaya, F. A. (2019). ASI Eksklusif: Nutrisi Ideal untuk Bayi 0-6 Bulan. Cermin Dunia Kedokteran, 46(4), 296–300. https://doi.org/10.55175/cdk.v46i4.485
Zhu, B., Zheng, S., Lin, K., Xu, X., Lv, L., Zhao, Z., & Shao, J. (2021). Effects of Infant Formula Supplemented With Prebiotics and OPO on Infancy Fecal Microbiota: A Pilot Randomized Clinical Trial. Frontiers in Cellular and Infection Microbiology, 11. https://doi.org/10.3389/fcimb.2021.650407
Altobelli, E., Angeletti, P. M., Verrotti, A., & Petrocelli, R. (2020). The Impact of Human Milk on Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis. Nutrients, 12(5). https://doi.org/10.3390/nu12051322
Batta, V. K., Rao, S. C., & Patole, S. K. (2023). Bifidobacterium infantis as a probiotic in preterm infants: a systematic review and meta-analysis. Pediatric Research, 94(6), 1887–1905. https://doi.org/10.1038/s41390-023-02716-w
Campos-Martinez, A. M., Expósito-Herrera, J., Gonzalez-Bolívar, M., Fernández-Marin, E., & Uberos, J. (2022). Evaluation of Risk and Preventive Factors for Necrotizing Enterocolitis in Premature Newborns. A Systematic Review of the Literature. Frontiers in Pediatrics, 10. https://doi.org/10.3389/fped.2022.874976
Colarelli, A. M., Barbian, M. E., & Denning, P. W. (2024). Prevention Strategies and Management of Necrotizing Enterocolitis. Current Treatment Options in Pediatrics, 10(3), 126–146. https://doi.org/10.1007/s40746-024-00297-2
Dombrowska-Pali, A., Wiktorczyk-Kapischke, N., Chrustek, A., Olszewska-Słonina, D., Gospodarek-Komkowska, E., & Socha, M. W. (2024). Human Milk Microbiome—A Review of Scientific Reports. Nutrients, 16(10), 1420. https://doi.org/10.3390/nu16101420
Duess, J. W., Sampah, M. E., Lopez, C. M., Tsuboi, K., Scheese, D. J., Sodhi, C. P., & Hackam, D. J. (2023). Necrotizing enterocolitis, gut microbes, and sepsis. Gut Microbes, 15(1). https://doi.org/10.1080/19490976.2023.2221470
Gates, A., Marin, T., Leo, G. De, & Stansfield, B. K. (2021). Review of Preterm Human‐Milk Nutrient Composition. Nutrition in Clinical Practice, 36(6), 1163–1172. https://doi.org/10.1002/ncp.10570
Handoyo. (2018). Necrotizing Enterocolitis pada Neonatus Prematur dan Suplementasi Probiotik. Cermin Dunia Kedokteran, 45(5), 391–394. https://doi.org/10.55175/cdk.v45i5.795
Hassinger, D., Clausen, D. M., Nitka, S., Herdt, A., & Griffin, I. (2020). Analysis of Disialyllacto-N-Tetraose (DSLNT) Content in Milk From Mothers of Preterm Infants. Journal of Human Lactation, 36(2), 291–298. https://doi.org/10.1177/0890334420904041
Iftinan, Y., Ranti Filarma Negara Purnama, Lale Srigading Udayanti, Izza Ahmad Muharis, Jannatul Cahya Admiyanti, & Yusra Pintaningrum. (2023). Enterokolitis Nekrotik: Patofisiologi, Diagnosis dan Tatalaksana. Lombok Medical Journal, 2(1), 1–4. https://doi.org/10.29303/lmj.v2i1.2390
Kaban, R. K., Rohsiswatmo, R., Kautsar, A., Sutrisno, A. A., Hikmahrachim, H. G., & Hardiyanti, N. (2022). Risk factors of necrotizing enterocolitis-related mortality and patient survival: a preliminary prospective study. Paediatrica Indonesiana(Paediatrica Indonesiana), 62(3), 175–180. https://doi.org/10.14238/pi62.3.2022.175-80
Kanuri, S. H., Bagang, N., Ulucay, A. S., & Singh, G. P. (2023). Is Intestinal Cell Death in Necrotising Enterocolitis Assorted and Multifarious? A Special Focus on Risk Factors and Their Pathogenic Mechanisms. EMJ Gastroenterology. https://doi.org/10.33590/emjgastroenterol/10303125
Luthfi Taufik, M., & Lestari, D. (2021). Diagnosis dan Tatalaksana Enterokolitis Nekrotikans. Cermin Dunia Kedokteran, 48(4), 225. https://doi.org/10.55175/cdk.v48i4.1366
Martinez, R. C. R., Bedani, R., & Saad, S. M. I. (2015). Scientific evidence for health effects attributed to the consumption of probiotics and prebiotics: an update for current perspectives and future challenges. British Journal of Nutrition, 114(12), 1993–2015. https://doi.org/10.1017/S0007114515003864
Masi, A. C., Beck, L. C., Perry, J. D., Granger, C. L., Hiorns, A., Young, G. R., Bode, L., Embleton, N. D., Berrington, J. E., & Stewart, C. J. (2024). Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis. Cell Reports Medicine, 5(9), 101708. https://doi.org/10.1016/j.xcrm.2024.101708
Masi, A. C., Embleton, N. D., Lamb, C. A., Young, G., Granger, C. L., Najera, J., Smith, D. P., Hoffman, K. L., Petrosino, J. F., Bode, L., Berrington, J. E., & Stewart, C. J. (2021). Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis. Gut, 70(12), 2273–2282. https://doi.org/10.1136/gutjnl-2020-322771
Niño, D. F., Sodhi, C. P., & Hackam, D. J. (2016). Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nature Reviews Gastroenterology & Hepatology, 13(10), 590–600. https://doi.org/10.1038/nrgastro.2016.119
O’Rourke, L., Clarke, G., Nolan, A., Watkins, C., Dinan, T. G., Stanton, C., Ross, R. P., & Ryan, C. A. (2018). Tryptophan metabolic profile in term and preterm breast milk: implications for health. Journal of Nutritional Science, 7, e13. https://doi.org/10.1017/jns.2017.69
Paré, G., & Kitsiou, S. (2017). Handbook of eHealth Evaluation: An Evidence-Based Approach (F. Lau & C. Kuziemsky, Eds.). University of Victoria.
Parker, L. A., Koernere, R., Fordham, K., Bubshait, H., Eugene, A., Gefre, A., & Bendixen, M. (2024). Mother’s Own Milk Versus Donor Human Milk. Critical Care Nursing Clinics of North America, 36(1), 119–133. https://doi.org/10.1016/j.cnc.2023.09.002
Poulimeneas, D., Bathrellou, E., Antonogeorgos, G., Mamalaki, E., Kouvari, M., Kuligowski, J., Gormaz, M., Panagiotakos, D. B., & Yannakoulia, M. (2021). Feeding the preterm infant: an overview of the evidence. International Journal of Food Sciences and Nutrition, 72(1), 4–13. https://doi.org/10.1080/09637486.2020.1754352
Sajankila, N., Wala, S. J., Ragan, M. V., Volpe, S. G., Dumbauld, Z., Purayil, N., Mihi, B., & Besner, G. E. (2023). Current and future methods of probiotic therapy for necrotizing enterocolitis. Frontiers in Pediatrics, 11. https://doi.org/10.3389/fped.2023.1120459
Sami, A. S., Frazer, L. C., Miller, C. M., Singh, D. K., Clodfelter, L. G., Orgel, K. A., & Good, M. (2023). The role of human milk nutrients in preventing necrotizing enterocolitis. Frontiers in Pediatrics, 11. https://doi.org/10.3389/fped.2023.1188050
Savarino, G., Carta, M., Cimador, M., Corsello, A., Giuffrè, M., Schierz, I. A. M., Serra, G., & Corsello, G. (2021). Necrotizing enterocolitis in the preterm: newborns medical and nutritional Management in a Single-Center Study. Italian Journal of Pediatrics, 47(1), 226. https://doi.org/10.1186/s13052-021-01180-8
Sharif, S., Oddie, S. J., Heath, P. T., & McGuire, W. (2023). Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. The Cochrane Database of Systematic Reviews, 6(6), CD015133. https://doi.org/10.1002/14651858.CD015133.pub2
Shaw, A. G., Sim, K., Rose, G., Wooldridge, D. J., Li, M.-S., Misra, R. V., Gharbia, S., & Kroll, J. S. (2021). Premature neonatal gut microbial community patterns supporting an epithelial TLR-mediated pathway for necrotizing enterocolitis. BMC Microbiology, 21(1), 225. https://doi.org/10.1186/s12866-021-02285-0
Shulhan, J., Dicken, B., Hartling, L., & Larsen, B. M. (2017). Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products. Advances in Nutrition, 8(1), 80–91. https://doi.org/10.3945/an.116.013193
Syahniar, R., & Suri, A. A. (2020). Profil Mikrobiota ASI dan Perannya terhadap Saluran Cerna Bayi. Muhammadiyah Journal of Nutrition and Food Science (MJNF), 1(1), 8. https://doi.org/10.24853/mjnf.1.1.8-17
Wijaya, F. A. (2019). ASI Eksklusif: Nutrisi Ideal untuk Bayi 0-6 Bulan. Cermin Dunia Kedokteran, 46(4), 296–300. https://doi.org/10.55175/cdk.v46i4.485
Zhu, B., Zheng, S., Lin, K., Xu, X., Lv, L., Zhao, Z., & Shao, J. (2021). Effects of Infant Formula Supplemented With Prebiotics and OPO on Infancy Fecal Microbiota: A Pilot Randomized Clinical Trial. Frontiers in Cellular and Infection Microbiology, 11. https://doi.org/10.3389/fcimb.2021.650407
Published
2025-09-30
How to Cite
PUTRI, Dyah Arista et al.
PROTECTIVE ROLE OF HUMAN BREAST MILK AGAINST NECROTIZING ENTEROCOLITIS IN PRETERM INFANTS.
Mandala Of Health, [S.l.], v. 18, n. 2, p. 234-246, sep. 2025.
ISSN 2615-6954.
Available at: <https://jos.unsoed.ac.id/index.php/mandala/article/view/17753>. Date accessed: 16 oct. 2025.
doi: https://doi.org/10.20884/1.mandala.2025.18.2.17753.
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Articles
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