Anti-viral Properties of Human Milk Oligosaccharides

  • Sugars found in human milk, called human milk oligosaccharides (HMOs), have been shown to protect against bacterial pathogens and viruses.
  • A new review provides an overview of evidence that HMOs might protect against viruses common in pediatric ICUs, including norovirus and respiratory syncytial virus.
  • The findings further highlight the benefits of breastfeeding in protecting infants, while also adding to the potential applications of HMOs.

 

A surge in viral infections this past summer caused more children to be hospitalized than usual, and it’s not all COVID-19 [1,2]. Other respiratory viruses, including respiratory syncytial virus, have been hitting kids hard, highlighting how vulnerable they can be to viral infections. So it’s a good thing that in addition to providing nutrition, human milk can help protect against these diseases. Sugars called human milk oligosaccharides (HMOs) are abundant in human milk and are one of the human milk components that have been shown to have protective effects against a wide range of pathogens.

Many studies have shown how HMOs protect against bacterial pathogens, and Dr. Steven Townsend of Vanderbilt University wondered whether there was also evidence for their effects against viruses. “We know these compounds have activity against bacteria, so I told my students to start to figure out what’s known in the literature about their antiviral properties,” he says. In a new review article, Townsend and his co-authors present an overview of evidence that HMOs might also protect against several viruses [3]. “It turns out that these compounds do have some interesting antiviral properties,” he says.

Viruses recognize and bind to sugars in our body during infection, and the review article highlights several examples of human milk sugars functioning as a receptor decoy for viral binding and thus preventing viral infection [3]. “These compounds look like a lot of sugars that are on human surfaces, whether it’s in our saliva, on the mucus layer, in our eyes, or on our epithelium, and they become very potent decoy receptors,” says Townsend.

Townsend and his colleagues listed examples of binding between certain HMOs, such as 2-fucosyllactose and 3-fucosyllactose, and several viruses, including influenza, rotavirus, respiratory syncytial virus, human immunodeficiency virus (HIV), and norovirus, as well as evidence of such binding reducing viral infection [114]. They also found evidence of a role for HMOs in modulating the immune response, which can reduce infection by these viruses and also prevent necrotizing enterocolitis (NEC), an intestinal disease linked to viral infections [1418]. Some studies have found disialyllacto-N-tetraose to be the most effective HMO in preventing NEC, although the underlying mechanism is still unclear [19,20].

High concentrations of HMOs present in breast milk have also been shown to reduce the risk of transmission of HIV to the infant through breastfeeding [13]. Researchers are also starting to look into whether SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is transmitted through breastfeeding, and whether HMOs can serve as receptor decoys or have other protective effects against this virus [21].

The review article suggests that the antiviral properties of HMOs may be worth investigating further [3]. Researchers still don’t fully understand the specific structural basis for HMOs’ antiviral properties, and only a small number of known HMOs have been structurally characterized or evaluated for antiviral activity.

Figuring out ways to synthesize more HMOs would help researchers better study the  link between their structure and their antiviral activity. “My group and others are figuring out ways to synthesize these compounds,” says Townsend. “I think if we’re careful and we’re smart, there are a lot of strategic applications for most of them,” he says.

The review highlights yet another way that human milk protects infants. “Breastfeeding is super powerful, and if you just go to the literature, you can see breastfed babies typically get sick far less than formula-fed babies, and HMOs are just a small part of that equation,” says Townsend. “Infant formula does not have HMOs, and there are companies that are trying to add them to formula, but they’re not adding 8 to 20 grams, so what we’re able to add at the moment is not even close to what moms can provide,” he says. So when it comes to protecting infants against infections, it seems like there’s no substitute for mother’s milk.

 

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2. Fox M, 2021. Respiratory infections other than Covid-19 are filling up pediatric wards. [online] CNN. Available at: <https://www.cnn.com/2021/08/26/health/respiratory-viruses-kids-rsv-rhinovirus-covid/index.html> [Accessed 18 October 2021].

3. Moore RE, Xu LL, Townsend SD. Prospecting human milk oligosaccharides as a defense against viral infections. ACS Infect Dis. 2021 Feb 12;7(2):254-63.

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7. Laucirica DR, Triantis V, Schoemaker R, Estes MK, Ramani S. Milk oligosaccharides inhibit human rotavirus infectivity in MA104 cells. J Nutr. 2017 Sep;147(9):1709-14.

8. Hester SN, Chen X, Li M, Monaco MH, Comstock SS, Kuhlenschmidt TB, Kuhlenschmidt MS, Donovan SM. Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets. Br J Nutr. 2013 Oct;110(7):1233-42.

9. Duska-McEwen G, Senft AP, Ruetschilling TL, Barrett EG, Buck RH. Human milk oligosaccharides enhance innate immunity to respiratory syncytial virus and influenza. Food Nutr Sci. 2014 Aug;5(14):1387−98.

10. van Liempt E, Bank CM, Mehta P, Garciá-Vallejo JJ, Kawar ZS, Geyer R, Alvarez RA, Cummings RD, Kooyk Yv, van Die I. Specificity of DC-SIGN for mannose- and fucose-containing glycans. FEBS Lett. 2006 Nov 13;580(26):6123-31.

11. Weichert S, Koromyslova A, Singh BK, Hansman S, Jennewein S, Schroten H, Hansman GS. Structural basis for norovirus inhibition by human milk oligosaccharides. J Virol. 2016 Apr 14;90(9):4843-48.

12. Shang J, Piskarev VE, Xia M, Huang P, Jiang X, Likhosherstov LM, Novikova OS, Newburg DS, Ratner DM. Identifying human milk glycans that inhibit norovirus binding using surface plasmon resonance. Glycobiology. 2013 Dec;23(12):1491-8.

13. Bode L, Kuhn L, Kim HY, Hsiao L, Nissan C, Sinkala M, Kankasa C, Mwiya M, Thea DM, Aldrovandi GM. Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding. Am J Clin Nutr. 2012 Oct;96(4):831-9.

14. Triantis V, Bode L, van Neerven RJJ. Immunological effects of human milk oligosaccharides. Front Pediatr. 2018 Jul 2;6:190.

15. Newburg DS, Ruiz-Palacios GM, Morrow AL. Human milk glycans protect infants against enteric pathogens. Annu Rev Nutr. 2005;25:37-58.

16. Le Doare K, Holder B, Bassett A, Pannaraj PS. Mother’s milk: A purposeful contribution to the development of the infant microbiota and immunity. Front Immunol. 2018 Feb 28;9:361.

17. Xiao L, Leusink-Muis T, Kettelarij N, van Ark I, Blijenberg B, Hesen NA, Stahl B, Overbeek SA, Garssen J, Folkerts G, Van’t Land B. Human milk oligosaccharide 2′-fucosyllactose improves innate and adaptive immunity in an influenza-specific murine vaccination model. Front Immunol. 2018 Mar 9;9:452.

18. Wiciński M, Sawicka E, Gębalski J, Kubiak K, Malinowski B. Human milk oligosaccharides: health benefits, potential applications in infant formulas, and pharmacology. Nutrients. 2020 Jan 20;12(1):266.

19. Bode L. Human milk oligosaccharides in the prevention of necrotizing enterocolitis: A journey from in vitro and in vivo models to mother-infant cohort studies. Front Pediatr. 2018 Dec 4;6:385.

20. Autran CA, Kellman BP, Kim JH, Asztalos E, Blood AB, Spence ECH, Patel AL, Hou J, Lewis NE, Bode L. Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants. Gut. 2018 Jun;67(6):1064-70.

21. Groß R, Conzelmann C, Müller JA, Stenger S, Steinhart K, Kirchhoff F, Münch J. Detection of SARS-CoV-2 in human breastmilk. Lancet. 2020 Jun 6;395(10239):1757-58.

 

Contributed by
Dr. Sandeep Ravindran
Freelance Science Writer
Sandeepr.com