Literature Review: Infant formulas with human milk oligosaccharides on gut microbiome and intestinal immune system

Author(s): Carissa Wira Amadea, A’immatul Fauziyah
DOI: 10.30867/gikes.v5i1.1378


Background: Infant formula has a similar composition to breast milk, especially on key components like proteins, fats, and functional oligosaccharides. However, significant differences exist between bovine milk-based formula and human breast milk, particularly in the abundance and diversity of human milk oligosaccharides (HMOs). HMOs are pivotal in shaping the infant gut microbiome and immune system, with potential implications for infant health and development.

Objectives: The literature review aimed to explore the role of HMOs in shaping the gut microbiome and strengthening the intestinal immune system in infants.

Methods: Descriptive research was carried out in May-August 2023 using the literature review method. The design and implementation of this study referred to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for Randomized Controlled Trials (RCTs). Literature sources were obtained from PubMed, Elsevier, Medline, Nature, PLOS, MPDI, JAMA, and Scopus publication databases with a limitation of the last ten years (2013-2023). One hundred twenty articles were obtained with these keywords and then selected in stages according to predetermined criteria. Six articles that met the criteria were retrieved from 2013-2023. The articles obtained were compiled, analyzed, and concluded by looking for similarities and dissimilarities, giving views, comparing, and summarizing.

Results: The review revealed that HMOs significantly influenced the composition and function of the infant's intestinal microbiota, inhibiting harmful pathogens in the intestine. Therefore, HMOs as prebiotics were crucial in promoting intestinal immune system health in infants.

Conclusion: Human Milk Oligosaccharides (HMOs) in infant formula substantially impacted the gut microbiome composition and the infant's intestinal immune system. Studies consistently showed that HMOs influenced the growth and diversity of gut bacteria, leading to outcomes similar to those seen in breastfed infants.


Human Milk, Gut Microbiota; Oligosaccharides; Intestinal Immune System, Infant Formula

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Akkerman, R., Faas, M. M., & de Vos, P. (2019). Non-digestible carbohydrates in infant formula as substitution for human milk oligosaccharide functions: Effects on microbiota and gut maturation. Critical Reviews in Food Science and Nutrition, 59(9), 1486–1497.

Alliet, P., Vandenplas, Y., Roggero, P., Jespers, S. N. J., Peeters, S., Stalens, J. P., Kortman, G. A. M., Amico, M., Berger, B., & Sprenger, N. (2022). Safety and efficacy of a probiotic containing infant formula supplemented with 2 ’ fucosyllactose : a double blind randomized controlled trial. Nutrition Journal, 1–16.

Ballard, O., & Morrow, A. L. (2013). Human Milk Composition. Nutrients and Bioactive Factors. Pediatric Clinics of North America, 60(1), 49–74.

Berger, B., Porta, N., Foata, F., Grathwohl, D., Delley, M., Moine, D., Charpagne, A., Siegwald, L., Descombes, P., Alliet, P., Puccio, G., Steenhout, P., Mercenier, A., & Sprenger, N. (2020). Linking human milk oligosaccharides, infant fecal community types, and later risk to require antibiotics. MBio, 11(2).

Bode, L. (2012). Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology, 22(9), 1147–1162.

Bosheva, M., Tokodi, I., Krasnow, A., Pedersen, H. K., Lukjancenko, O., Eklund, A. C., Grathwohl, D., Sprenger, N., Berger, B., & Cercamondi, C. I. (2022). Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial. Frontiers in Nutrition, 9(July), 1–14.

Bych, K., Mikš, M. H., Johanson, T., Hederos, M. J., Vigsnæs, L. K., & Becker, P. (2019). Production of HMOs using microbial hosts — from cell engineering to large scale production. Current Opinion in Biotechnology, 56, 130–137.

Chahyanto, B. A., Pandiangan, D., Aritonang, E. S., & Laruska, M. (2019). Pemberian informasi dasar Posyandu melalui kegiatan penyegaran kader dalam meningkatkan pengetahuan kader di Puskesmas Pelabuhan Sambas Kota Sibolga. AcTion: Aceh Nutrition Journal, 4(1), 7–14.

Dinleyici, M., Barbieur, J., Dinleyici, E. C., & Vandenplas, Y. (2023). Functional effects of human milk oligosaccharides (HMOs). Gut Microbes, 15(1).

Donovan, S. M., Wallingford, J. C., & Myers, P. N. (2022). Effects of addition of 2-fucosyllactose to infant formula on growth and specific pathways of utilization by Bifidobacterium in healthy term infants. September.

Dorothy L. Ackerman, K. M., Craft, Ryan S. Doster, J., Hendrik Weitkamp, D. M., Aronoff, J. A. G., & Townsend, S. D. (2018). Antimicrobial and Antibiofilm Activity of Human Milk Oligosaccharides against Streptococcus agalactiae, Staphylococcus aureus, and Acinetobacter baumannii Dorothy. 4(3), 1–10.

EFSA NDA Panel. (2015). Safety of 2′-O-fucosyllactose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFSA Journal, 13(7).

Hill, D. R., & Buck, R. H. (2023). Infants Fed Breastmilk or 2 -FL Supplemented Formula Have Similar Systemic Levels of Microbiota-Derived Secondary Bile Acids.

Hoeflinger, J. L., Davis, S. R., Chow, J. M., & Miller, M. J. (2015). In vitro impact of human milk oligosaccharides on Enterobacteriaceae growth. Journal of Agricultural and Food Chemistry, 63(12), 3295–3302.

Kavanaugh, M. L., Jerman, J., & Finer, L. B. (2015). Changes in use of long-acting reversible contraceptive methods among U.S. Women, 2009-2012. Obstetrics and Gynecology, 126(5), 917–927.

Kulinich, A., & Liu, L. (2016). Human milk oligosaccharides: The role in the fine-tuning of innate immune responses. Carbohydrate Research, 432, 62–70.

Levitt, H. M., Bamberg, M., Creswell, J. W., Frost, D. M., Josselson, R., & Suárez-Orozco, C. (2018). Journal article reporting standards for qualitative primary, qualitative meta-analytic, and mixed methods research in psychology: The APA Publications and Communications Board task force report. American Psychologist, 73(1), 26.

Levy, O., & Wynn, J. L. (2014). A prime time for trained immunity: Innate immune memory in newborns and infants. Neonatology, 105(2), 136–141.

Li, M., Monaco, M. H., Wang, M., Comstock, S. S., Kuhlenschmidt, T. B., Fahey, G. C., Miller, M. J., Kuhlenschmidt, M. S., & Donovan, S. M. (2014). Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota. ISME Journal, 8(8), 1609–1620.

Makar, G., Foltz, C., Lendner, M., & Vaccaro, A. R. (2018). How to Write Effective Discussion and Conclusion Sections. Clinical Spine Surgery, 31(8), 345–346. 10.1097/BSD.0000000000000687

Markowiak, P., & Ślizewska, K. (2017). Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients, 9(9).

Masic, I. (2018). How to Write an Efficient Discussion? Medical Archives, 72(4), 306.

McGuire, M. K., Meehan, C. L., McGuire, M. A., Williams, J. E., Foster, J., Sellen, D. W., Kamau-Mbuthia, E. W., Kamundia, E. W., Mbugua, S., Moore, S. E., Prentice, A. M., Kvist, L. J., Otoo, G. E., Brooker, S. L., Price, W. J., Shafii, B., Placek, C., Lackey, K. A., Robertson, B., … Bode, L. (2017). What’s normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically. American Journal of Clinical Nutrition, 105(5), 1086–1100.

Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. BMJ, 339(7716), 332–336.

Motee, A., & Jeewon, R. (2014). Importance of exclusive breast feeding and complementary feeding among infants. Current Research in Nutrition and Food Science, 2(2), 56–72.

Newburg, D. S., & Grave, G. (2014). Recent advances in human milk glycobiology. Pediatric Research, 75(5), 675–679.

Ruhaak, L. R., Stroble, C., Underwood, M. A., & Lebrilla, C. B. (2014). Detection of milk oligosaccharides in plasma of infants. Analytical and Bioanalytical Chemistry, 406(24), 5775–5784.

Soyyilmaz, B., Mikš, M. H., Röhrig, C. H., Matwiejuk, M., Meszaros‐matwiejuk, A., & Vigsnæs, L. K. (2021). The mean of milk: A review of human milk oligosaccharide concentrations throughout lactation. Nutrients, 13(8), 1–22.

Storm, H. M., Shepard, J., Czerkies, L. M., Kineman, B., Cohen, S. S., Reichert, H., & Carvalho, R. (2019). 2 ′ -Fucosyllactose Is Well Tolerated in a 100 % Whey , Partially Hydrolyzed Infant Formula With Bifidobacterium lactis : A Randomized Controlled Trial.

Thongaram, T., Hoeflinger, J. L., Chow, J. M., & Miller, M. J. (2017). Human milk oligosaccharide consumption by probiotic and human-associated bifidobacteria and lactobacilli. Journal of Dairy Science, 100(10), 7825–7833.

Vandenplas, Y., Berger, B., Carnielli, V. P., Ksiazyk, J., Lagström, H., Luna, M. S., Migacheva, N., Mosselmans, J. M., Picaud, J. C., Possner, M., Singhal, A., & Wabitsch, M. (2018). Human milk oligosaccharides: 2’-fucosyllactose (2’-FL) and lacto-n-neotetraose (LNnT) in infant formula. Nutrients, 10(9).

Walker, W. A., & Iyengar, R. S. (2015). Breast milk, microbiota, and intestinal immune homeostasis. Pediatric Research, 77(1), 220–228.

Walsh, C., Lane, J. A., van Sinderen, D., & Hickey, R. M. (2020). Human milk oligosaccharides: Shaping the infant gut microbiota and supporting health. Journal of Functional Foods, 72(July), 104074.

Wang, M., Monaco, M. H., & Donovan, S. M. (2016). Impact of early gut microbiota on immune and metabolic development and function. Seminars in Fetal and Neonatal Medicine, 21(6), 380–387.

Wicinski, M., Sawicka, E., Gebalski, J., Kubiak, K., & Malinowski, B. (2020). Human Milk Oligosaccharides : Health Benefits , and Pharmacology. Nutrients, 12(266), 1–14.

Yu, Z. T., Nanthakumar, N. N., & Newburg, D. S. (2016). The human milk oligosaccharide 2’-fucosyllactose quenches Campylobacter jejuni-induced inflammation in human epithelial cells HEp-2 and HT-29 and in mouse intestinal Mucosa1-3. Journal of Nutrition, 146(10), 1980–1990.


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