After lactose and fat, HMOs are the third largest component of human milk solids, at 8 percent ¹³⁸Soyyilmaz, 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. https://doi.org/10.3390/nu13082737. HMOs are non-digestible carbohydrates that help provide the optimum conditions for beneficial bacteria to thrive in the infant gut and play an important role in supporting the immune system and contributing to brain development ¹⁶Bode L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology. Published online 2012. doi:10.1093/glycob/cws074 ¹⁵Bode, L., Kuhn, L., Kim, H.-Y., Hsiao, L., Nissan, C., Sinkala, M., Kankasa, C., Mwiya, M., Thea, D. M., & Aldrovandi, G. M. (2012). Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding. The American Journal of Clinical Nutrition, 96(4), 831–839. https://doi.org/10.3945/ajcn.112.039503 ¹⁴Bode, L., & Jantscher-Krenn, E. (2012). Structure-function relationships of human milk oligosaccharides. Advances in Nutrition. https://doi.org/10.3945/an.111.001404. So far, more than 200 different HMOs have been identified at various concentrations and combinations in breast milk ⁴⁶German, J., Freeman, S., Lebrilla, C., & Mills, D. (2008). Human milk oligosaccharides: Evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutrition Workshop Series: Pediatric Program. https://doi.org/10.1159/000146322. These include 2’-FL, 3’-SL and LNT, each of which is expected to have its own potential benefits for infant health.

Research shows that HMOs have an important role to play by supporting infant health in various ways. These include influencing the gut microbiome, reducing the risk of infection and supporting the brain development of infants ¹⁶Bode L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology. Published online 2012. doi:10.1093/glycob/cws074 ¹⁵Bode, L., Kuhn, L., Kim, H.-Y., Hsiao, L., Nissan, C., Sinkala, M., Kankasa, C., Mwiya, M., Thea, D. M., & Aldrovandi, G. M. (2012). Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding. The American Journal of Clinical Nutrition, 96(4), 831–839. https://doi.org/10.3945/ajcn.112.039503 ¹⁴Bode, L., & Jantscher-Krenn, E. (2012). Structure-function relationships of human milk oligosaccharides. Advances in Nutrition. https://doi.org/10.3945/an.111.001404. Different individual HMOs have been shown to have different effects ⁷Asakuma, S., Hatakeyama, E., Urashima, T., Yoshida, E., Katayama, T., Yamamoto, K., Kumagai, H., Ashida, H., Hirose, J., & Kitaoka, M. (2011). Physiology of consumption of human milk oligosaccharides by infant gut-associated bifidobacteria. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M111.248138 ¹⁴Bode, L., & Jantscher-Krenn, E. (2012). Structure-function relationships of human milk oligosaccharides. Advances in Nutrition. https://doi.org/10.3945/an.111.001404 ⁸⁹Lin, A. E., Autran, C. A., Szyszka, A., Escajadillo, T., Huang, M., Godula, K., Prudden, A. R., Boons, G. J., Lewis, A. L., Doran, K. S., Nizet, V., & Bode, L. (2017). Human milk oligosaccharides inhibit growth of group B Streptococcus. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M117.789974 ¹³⁰Salli, K., Hirvonen, J., Siitonen, J., Ahonen, I., Anglenius, H., & Maukonen, J. (2021). Selective Utilization of the Human Milk Oligosaccharides 2′-Fucosyllactose, 3-Fucosyllactose, and Difucosyllactose by Various Probiotic and Pathogenic Bacteria. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/acs.jafc.0c06041 ¹⁵⁶Watson, D., O’Connell Motherway, M., Schoterman, M. H. C., van Neerven, R. J. J., Nauta, A., & Van Sinderen, D. (2013). Selective carbohydrate utilization by lactobacilli and bifidobacteria. Journal of Applied Microbiology. https://doi.org/10.1111/jam.12105 ¹⁷⁰Yu, Z. T., Chen, C., Kling, D. E., Liu, B., McCoy, J. M., Merighi, M., Heidtman, M., & Newburg, D. S. (2013). The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota. Glycobiology. https://doi.org/10.1093/glycob/cws138 , so they may complement each other in supporting infant health.

At FrieslandCampina Ingredients, we believe that delivering a larger variety of non-digestible oligosaccharides (e.g. a combination of GOS and HMOs) can be of key importance for the establishment of the gut microbiota and its metabolism, thereby feeding into many different health aspects in early life and beyond. As a unique provider of both GOS and HMO solutions, we can offer a wider diversity of structures to bring the concept of gut health to the next level.

• 2’-Fucosyllactose (2’-FL) is a fucosylated HMO
• Most abundant HMO in human milk ²¹Chaturvedi, P., Warren, C. D., Altaye, M., Morrow, A. L., Ruiz-Palacios, G., Pickering, L. K., & Newburg, D. S. (2001). Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology, 11(5), 365–372.
• Stimulation of the growth of beneficial Bifidobacteria in vitro ¹⁶⁹Yu, Z. T., Chen, C., & Newburg, D. S. (2013). Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes. Glycobiology, 23(11), 1281–1292.https://doi.org/10.1093/glycob/cwt065
• An association study demonstrated that infants receiving breast milk with high 2’-FL content show enhanced gut colonisation with Bifidobacterium as compared with infants receiving milk without 2’-FL ⁸⁸Lewis, Z. T., Totten, S. M., Smilowitz, J. T., Popovic, M., Parker, E., Lemay, D. G., Van Tassell, M. L., Miller, M. J., Jin, Y.-S., German, J. B., Lebrilla, C. B., & Mills, D. A. (2015). Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome, 3(1), 13.https://doi.org/10.1186/s40168-015-0071-z
• Pre-clinical research has shown that 2’-FL can inhibit adhesion and infectivity of the diarrhea pathogens norovirus, rotavirus, EPEC, Campylobacter jejuni and Salmonella enterica serovar fyris, as well as the respiratory tract infection pathogen Pseudomonas aeruginosa ⁸⁵Laucirica, D. R., Triantis, V., Schoemaker, R., Estes, M. K., & Ramani, S. (2017). Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells. Journal of Nutrition, 147(9), 1709–1714 ¹⁵⁷Weichert, S., Jennewein, S., Hüfner, E., Weiss, C., Borkowski, J., Putze, J., & Schroten, H. (2013). Bioengineered 2’-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines. Nutrition Research (New York, N.Y.), 33(10), 831–838.https://doi.org/10.1016/j.nutres.2013.07.009 ¹⁵⁸Weichert, S., Koromyslova, A., Singh, B. K., Hansman, S., Jennewein, S., Schroten, H., & Hansman, G. S. (2016). Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides. Journal of Virology, 90(9), 4843–4848.https://doi.org/10.1128/JVI.03223-15 ¹⁷¹Yu, 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. J Nutr, Epub.https://doi.org/10.3945/jn.116.230706.The. Association studies have shown that infants receiving breast milk with high 2’-FL content have a lower risk of Campylobacter jejuni-induced diarrhea ¹⁰³Morrow, A. L., Ruiz-Palacios, G. M., Altaye, M., Jiang, X., Guerrero, M. L., Meinzen-Derr, J. K., Farkas, T., Chaturvedi, P., Pickering, L. K., & Newburg, D. S. (2004). Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. The Journal of Pediatrics, 145(3), 297–303.https://doi.org/10.1016/j.jpeds.2004.04.054
• Recent clinical studies have shown that addition of 2’-FL to infant formula is safe and well tolerated by healthy infants ⁹⁶Marriage, B. J., Buck, R. H., Goehring, K. C., Oliver, J. S., & Williams, J. A. (2015). Infants Fed a Lower Calorie Formula with 2 ′ FL Show Growth and 2 ′ FL Uptake Like Breast-Fed Infants. Journal of Pediatric Gastroenterology and Nutrition.https://doi.org/10.1097/MPG.0000000000000889 ¹²¹Puccio, G., Alliet, P., Cajozzo, C., Janssens, E., Corsello, G., Sprenger, N., Wernimont, S., Egli, D., Gosoniu, L., & Steenhout, P. (2017). Effects of infant formula with human milk oligosaccharides on growth and morbidity: A randomized multicenter trial. Journal of Pediatric Gastroenterology and Nutrition.https://doi.org/10.1097/MPG.0000000000001520 ¹⁵⁰Vandenplas, Y., de Halleux, V., Arciszewska, M., Lach, P., Pokhylko, V., Klymenko, V., Schoen, S., Abrahamse-Berkeveld, M., Mulder, K. A., & Rubio, R. P. (2020). A partly fermented infant formula with postbiotics including 3′-GL, specific oligosaccharides, 2′-FL, and milk fat supports adequate growth, is safe and well-tolerated in healthy term infants: A double-blind, randomised, controlled, multi-country trial. Nutrients.https://doi.org/10.3390/nu12113560
• First efficacy outcomes from safety studies in infants suggest that 2’-FL can contribute to reducing the risk of respiratory tract infections ¹²¹Puccio, G., Alliet, P., Cajozzo, C., Janssens, E., Corsello, G., Sprenger, N., Wernimont, S., Egli, D., Gosoniu, L., & Steenhout, P. (2017). Effects of infant formula with human milk oligosaccharides on growth and morbidity: A randomized multicenter trial. Journal of Pediatric Gastroenterology and Nutrition.https://doi.org/10.1097/MPG.0000000000001520 and can have immunomodulatory activity ⁵⁰Goehring, K. C., Marriage, B. J., Oliver, J. S., Wilder, J. A., Barrett, E. G., & Buck, R. H. (2016). Similar to those who are breastfed, infants fed a formula containing 2’-fucosyllactose have lower inflammatory cytokines in a randomized controlled trial. Journal of Nutrition.https://doi.org/10.3945/jn.116.236919
• Pre-clinical research has shown a potential role of 2’-FL in brain development, cognition and learning ¹¹²Oliveros, E., Ramirez, M., Vazquez, E., Barranco, A., Gruart, A., Delgado-Garcia, J. M., Buck, R., Rueda, R., & Martin, M. J. (2016). Oral supplementation of 2’-fucosyllactose during lactation improves memory and learning in rats. Journal of Nutritional Biochemistry.https://doi.org/10.1016/j.jnutbio.2015.12.014 ¹⁵³Vazquez, E., Barranco, A., Ramirez, M., Gruart, A., Delgado-Garcia, J. M., Jimenez, M. L., Buck, R., & Rueda, R. (2016). Dietary 2′-fucosyllactose enhances operant conditioning and long-term potentiation via gut-brain communication through the vagus nerve in rodents. PLoS ONE.https://doi.org/10.1371/journal.pone.0166070 ¹⁵²Vázquez, E., Barranco, A., Ramírez, M., Gruart, A., Delgado-García, J. M., Martínez-Lara, E., Blanco, S., Martín, M. J., Castanys, E., Buck, R., Prieto, P., & Rueda, R. (2015). Effects of a human milk oligosaccharide, 2′-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents. Journal of Nutritional Biochemistry.https://doi.org/10.1016/j.jnutbio.2014.11.016
• 2’-FL in breast milk has been positively associated with cognitive outcomes and motor skill scores in 18-month-old children ¹¹³Oliveros, E., Martin, M., Torres-Espinola, F. J., Segura-Moreno, T., Ramirez, M., Santos-Fandila, A., Buck, R., Rueda, R., Escudero, M., Catena, A., Azaryah, H., & Campoy, C. (2021). Human Milk Levels of 2´-Fucosyllactose and 6´-Sialyllactose are Positively Associated with Infant Neurodevelopment and are Not Impacted by Maternal BMI or Diabetic Status. Nutrition &Food Science.

• Lacto-N-Tetraose (LNT) is a non-fucosylated HMO
• Most abundant neutral non-fucosylated HMO in human milk ¹³⁸Soyyilmaz, 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. https://doi.org/10.3390/nu13082737
• Enhancement of beneficial Bifidobacteria growth in vitro ⁷Asakuma, S., Hatakeyama, E., Urashima, T., Yoshida, E., Katayama, T., Yamamoto, K., Kumagai, H., Ashida, H., Hirose, J., & Kitaoka, M. (2011). Physiology of consumption of human milk oligosaccharides by infant gut-associated bifidobacteria. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M111.248138
• Pre-clinical research has shown that LNT can reduce growth, biofilm production and infectivity of Streptococcus Group B and Entamoeba histolytica. ²⁵Craft, K. M., Thomas, H. C., & Townsend, S. (2019). Sialylated Variants of Lacto-N-Tetraose Exhibit Antimicrobial Activity Against Group B Streptococcus. Organic & Biomolecular Chemistry, 17(7), 1893–1900. http://pubs.rsc.org/en/Content/ArticleLanding/2018/OB/C8OB02080A ⁷⁰Jantscher-Krenn, E., Lauwaet, T., Bliss, L. A., Reed, S. L., Gillin, F. D., & Bode, L. (2012). Human milk oligosaccharides reduce Entamoeba histolytica attachment and cytotoxicity in vitro. British Journal of Nutrition, 108(10), 1839–1846. https://doi.org/10.1017/S0007114511007392 ⁸⁹Lin, A. E., Autran, C. A., Szyszka, A., Escajadillo, T., Huang, M., Godula, K., Prudden, A. R., Boons, G. J., Lewis, A. L., Doran, K. S., Nizet, V., & Bode, L. (2017). Human milk oligosaccharides inhibit growth of group B Streptococcus. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M117.789974
• Sample material available

• 3’-Sialyllactose (3’-SL) is an acidic HMO
• In vitro research indicated that 3’-SL has antiviral and antibacterial effects against rotavirus, RSV (respiratory syncytial virus), influenza virus and UPEC ³⁰Duska-McEwen, G., Senft, A. P., Ruetschilling, T. L., Barrett, E. G., & Buck, R. H. (2014). Human Milk Oligosaccharides Enhance Innate Immunity to Respiratory Syncytial Virus and Influenza. Food and Nutrition Sciences, 5(14), 1387–1398.https://doi.org/10.4236/fns.2014.514151 ⁸⁵Laucirica, D. R., Triantis, V., Schoemaker, R., Estes, M. K., & Ramani, S. (2017). Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells. Journal of Nutrition, 147(9), 1709–1714 ⁹⁸Martin-Sosa, Samuel, Maria-Jesus, Hueso, M. ;, & Pablo. (2002). The sialylated fraction of milk oligosaccharides is Partially Responsible for Binding to Enterotoxigenic and Uropathogenic Escherichia coli Human Strains. The Journal of Nutrition, 132(10), 3067–3072. ¹²⁰Pandey, R. P., Kim, D. H., Woo, J., Song, J., Jang, S. H., Kim, J. B., Cheong, K. M., Oh, J. S., & Sohng, J. K. (2018). Broad-spectrum neutralization of avian influenza viruses by sialylated human milk oligosaccharides: in vivo assessment of 3′-sialyllactose against H9N2 in chickens. Scientific Reports, (1), 2563.https://doi.org/10.1038/s41598-018-20955-4
• Reduced inflammatory response was shown in pre-clinical experiments ⁵⁸Hyder, A. (2020). Dietary oligosaccharides attenuate DSS-induced colitis in mice, induce PGlyRP3 expression, and inhibit NF-κB and MEK/ERK signaling. Cellular Immunology, 354(February), 104144.https://doi.org/10.1016/j.cellimm.2020.104144 ⁷⁶Kang, L.-J., Kwon, E.-S., Lee, K. M., Cho, C., Lee, J.-I., Ryu, Y. B., Youm, T. H., Jeon, J., Cho, M. R., Jeong, S., Lee, S.-R., Kim, W., & Yang, S. (2018). 3’-Sialyllactose as an inhibitor of p65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis. Br J Pharmacol, Epub.
• 3’-SL contains sialic acid which is involved in early life brain development ²³Cho, S., Zhu, Z., Li, T., Baluyot, K., Howell, B. R., Hazlett, H. C., Elison, J. T., Hauser, J., Sprenger, N., Wu, D., & Lin, W. (2021). Human milk 3’-Sialyllactose is positively associated with language development during infancy. American Journal of Clinical Nutrition.https://doi.org/10.1093/ajcn/nqab103 ⁶⁸Jacobi, S. K., Yatsunenko, T., Li, D., Dasgupta, S., Yu, R. K., Berg, B. M., Chichlowski, M., & Odle, J. (2016). Dietary Isomers of Sialyllactose Increase Ganglioside Sialic Acid Concentrations in the Corpus Callosum and Cerebellum and Modulate the Colonic Microbiota of Formula-Fed Piglets1–3. The Journal of Nutrition, 146(2), 200–208.https://doi.org/10.3945/jn.115.220152 ¹⁵⁵Wang, B. (2012). Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Advances in Nutrition.https://doi.org/10.3945/an.112.001875
• Levels of 3’-SL in breast milk have been associated positively with language development in infants ²³Cho, S., Zhu, Z., Li, T., Baluyot, K., Howell, B. R., Hazlett, H. C., Elison, J. T., Hauser, J., Sprenger, N., Wu, D., & Lin, W. (2021). Human milk 3’-Sialyllactose is positively associated with language development during infancy. American Journal of Clinical Nutrition.https://doi.org/10.1093/ajcn/nqab103

With over 75 years of expertise in early life nutrition, we offer an industry-leading portfolio of oligosaccharides, along with a complete offering of nutritional ingredients for infant and young child milk formulas. Our fully owned and scalable HMO supply chain ensures the highest quality standards for dry-blend infant formula and has the flexibility to meet your needs as they evolve. We support leading global infant milk formula brands with our strong analytical expertise, helping to develop and validate analytical methods to ensure the right blend of HMOs and other ingredients for your product.