Written by: Sandeep Ravindran, Ph.D. | Issue # 89 | 2019
- Antibodies in human milk help protect infants from pathogens and may be particularly crucial for preterm infants.
- A new study finds that antibodies in a mother’s own milk survive digestion in the infant gut better than antibodies from donor breast milk, potentially increasing their effectiveness against pathogens.
- Human milk antibodies are more stable in preterm infants than in term infants, with preterm infant guts partially degrading IgA but not IgG and IgM.
- Antibody survival also depends on the specificity of the antibody against different pathogens.
Maternal antibodies play an important role in protecting newborns from harmful pathogens. Antibodies known as immunoglobulins (Igs) are transferred from the mother’s placenta into the fetus, where they protect the infant while the infant’s immune system is still developing [1].
Human milk also contains many different Igs, such as IgA, IgM, IgG, and secretory forms of IgA and IgM [2-4]. Consuming human milk provides additional immune protection to infants and has been shown to reduce the risk of infectious diseases [5].
The protective effect of maternal milk antibodies may be particularly crucial in a preterm infant, whose immune system is relatively underdeveloped [6,7]. “Pre-term infants have an immature immune system, and it’s particularly essential for these immunoglobulins to survive and fight against infection,” says Dr. Veronique Demers-Mathieu at Medolac Laboratories [Boulder City, NV]. “The overall aim of my research is to improve the immunity and growth and development of premature infants,” she says.
Demers-Mathieu was a postdoctoral researcher with Dr. David Dallas at Oregon State University, Corvallis, OR when they decided to investigate the survival of human milk antibodies in the infant gut. “In order to have activity to bind to pathogens or toxins, the antibodies need to survive across digestion and be intact,” says Demers-Mathieu. “Knowing what’s present in the gut is really important,” says Dallas.
Mothers of pre-term infants are often unable to provide all the milk required to feed their infants, and they supplement their infants with human milk received from donors [8]. However, donor milk undergoes extensive processing, including pooling of milk from different mothers, multiple freeze-thaw cycles, and pasteurization to inactivate viruses and kill bacteria [9-11]. All these steps may affect the survival and activity of antibodies present in donor milk.
In a new study, Demers-Mathieu and Dallas found that antibodies in mother’s own milk survived digestion in the infant gut better than antibodies from donor breast milk [12]. “Total IgA, secretory IgA, total IgM and IgG concentrations were higher in mother’s own milk than in pasteurized donor breast milk, and were higher in gastric contents when infants were fed mother’s breast milk than when infants were fed donor breast milk,” says Demers-Mathieu.
The findings suggest that feeding infants donor milk rather than their mother’s own milk could affect their immunity. “The higher concentration of antibodies in mother’s own breast milk than in pasteurized donor breast milk may make mother’s breast milk more effective in preventing enteric pathogen adhesion and invasion in newborns compared with donor milk,” says Demers-Mathieu. There is some previous evidence showing that preterm infants fed donor milk may have lower protection against pathogens [13,14].
The new study adds to our knowledge of the many different factors that influence the survival of antibodies in the infant gut. “It’s complex, there is a lot of digestion that occurs in the stomach and intestine, and it varies between different types of antibodies,” says Dallas.
Demers-Mathieu and Dallas previously found that preterm infants partially degrade IgA but not IgG and IgM in the stomach, and overall the stability of human milk antibodies was higher in preterm infants than in term infants [4,15]. “This could be beneficial for assisting the preterm infants’ immature immune system,” says Demers-Mathieu.
The researchers have also studied antibodies specific to different pathogens, and recently examined the survival of anti-pertussis and anti-influenza A-specific antibodies [16]. “The way that flu IgA degrades differs from the way that pertussis IgA does,” says Dallas. “The takeaway is that if you want to use an oral antibody to help prevent infection in babies, it’s really important to do this kind of work to see how much survives and figure out how to appropriately dose the antibody,” he says.
For instance, the researchers found that anti-influenza A-specific antibodies had a higher relative abundance in mother’s milk compared with donor’s milk [16]. “This suggests that supplementation of anti-influenza A-specific antibodies in donor milk may help reduce the risk of influenza virus infection,” says Dallas.
Levels of human milk antibodies also vary between different mothers. “Antibodies vary widely in raw human milk between mothers, which could be due to different maternal background, nutritional and environmental factors, as well as potential unknown factors,” says Demers-Mathieu. “The dose required of human milk antibodies to induce a significant protective effect against pathogens and their toxins remains unknown,” she says. “Studies are needed to determine the minimum effective dose in addition to important maternal factors that may influence the concentration of antibodies in raw human milk,” says Demers-Mathieu.
Studying the immune components of human milk could help develop new immune supplements to protect infants from pathogens. “My long-term goal is to identify the function of human milk immune components to protect against infection and pediatric diseases in premature infants,” says Demers-Mathieu. “We would like to develop new supplements with active immune components to add to donor milk as well as in mother’s milk with low level of immune components.”
References
1. Palmeira P., Quinello C., Silveira-Lessa A.L., Zago C.A., Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646.
2. Chandra R. Immunoglobulin and protein levels in breast milk produced by mothers of preterm infants. Nutr Res. 1982;2(1):27–30.
3. Goldman A.S., Garza C., Nichols B.L., Goldblum R.M. Immunologic factors in human milk during the first year of lactation. J Pediatr. 1982 Apr;100(4):563-7.
4. Demers-Mathieu V., Underwood M.A., Beverly R.L., Nielsen S.D., Dallas D.C. Comparison of human milk immunoglobulin survival during gastric digestion between preterm and term infants. Nutrients. 2018 May 17;10(5). pii: E631.
5. Duijts L., Jaddoe V.W., Hofman A., Moll H.A. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics. 2010 Jul;126(1):e18-25.
6. Zemlin M., Hoersch G., Zemlin C., Pohl-Schickinger A., Hummel M., Berek C., Maier R.F., Bauer K. The postnatal maturation of the immunoglobulin heavy chain IgG repertoire in human preterm neonates is slower than in term neonates. J Immunol. 2007 Jan 15;178(2):1180-8.
7. Malek A., Sager R., Kuhn P., Nicolaides K.H., Schneider H. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. 1996 Nov;36(5):248-55.
8. Carroll K., Herrmann K.R. The cost of using donor human milk in the NICU to achieve exclusively human milk feeding through 32 weeks postmenstrual age. Breastfeed Med. 2013 Jun;8(3):286-90.
9. Orloff S.L., Wallingford J.C., McDougal J.S. Inactivation of human immunodeficiency virus type I in human milk: Effects of intrinsic factors in human milk and of pasteurization. J Hum Lact. 1993 Mar;9(1):13-7.
10. Hamprecht K., Maschmann J., Müller D., Dietz K., Besenthal I., Goelz R., Middeldorp J.M., Speer C.P., Jahn G. Cytomegalovirus (CMV) inactivation in breast milk: Reassessment of pasteurization and freeze-thawing. Pediatr Res. 2004 Oct;56(4):529-35.
11. Franklin J.G. A comparison of the bactericidal efficiencies of laboratory Holder and HTST methods of milk pasteurization and the keeping qualities of the processed milks. Int J Dairy Technol. 1965 Apr;18(2):115–8.
12. Demers-Mathieu V., Huston R.K., Markell A.M., McCulley E.A., Martin R.L., Spooner M., Dallas D.C. Differences in maternal immunoglobulins within mother’s own breast milk and donor breast milk and across digestion in preterm infants. Nutrients. 2019 Apr 24;11(4). pii: E920.
13. Narayanan I., Murthy N.S., Prakash K., Gujral V.V. Randomised controlled trial of effect of raw and Holder pasteurised human milk and of formula supplements on incidence of neonatal infection. Lancet. 1984 Nov 17;2(8412):1111-3.
14. Schanler R.J., Lau C., Hurst N.M., Smith E.O.B. Randomized trial of donor human milk versus preterm formula as substitutes for mothers’ own milk in the feeding of extremely premature infants. Pediatrics. 2005 Aug;116(2):400-6.
15. Demers-Mathieu V., Underwood M.A., Beverly R.L., Dallas D.C. Survival of immunoglobulins from human milk to preterm infant gastric samples at 1, 2, and 3 h postprandial. Neonatology. 2018;114(3):242-50.
16. Demers-Mathieu V., Huston R.K., Markell A.M., McCulley E.A., Martin R.L., Dallas D.C. Antenatal influenza A-specific IgA, IgM, and IgG antibodies in mother’s own breast milk and donor breast milk, and gastric contents and stools from preterm infants. Nutrients. 2019;11(7): 1567-78.