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Recombinant Lactoferrin

Lactoferrin is one of the miraculous substances found in breastmilk which helps the infant kill bacteria and fight infection.  It is the major whey protein in human milk and has its highest concentrations in colostrum.  While it is important for all infants, it is especially important in the prevention of necrotizing enterocolitis (NEC) in preterm infants.   Lactoferrin has an anti-inflammatory action that may mitigate the pro-inflammatory states present in the gut before the onset of NEC.  This highlights the importance of mothers providing early feedings of colostrum and fresh mature milk to prevent necrotizing enterocolitis in their premature infant.

Researchers are experimenting with recombinant lactoferrin use in preterm infants and showing a benefit in reducing NEC.  In recombinant DNA, molecules of DNA are recombined into sequences that would not otherwise be found in the genome.   Recombining DNA is possible because DNA molecules from all organisms share the same chemical structure. They differ only in the nucleotides, the subunits of DNA and RNA, in the gene sequence.

Lactoferrin is present in cow’s milk in lower levels than found in human milk.  And the process of creating formula lowers those levels even further.  So, exogenous sources of lactoferrin must be added to formula if it is to match human levels.  Recombinant human lactoferrin can now be obtained from yeast, transgenic cows, and rice which have structural similarity to endogenous lactoferrin. 

There is already an infant formula manufacturer which is marketing Enspire™ containing lactoferrin in the range found in mature breastmilk.  This formula uses bovine sourced lactoferrin and is being marketed for use in any baby, not necessarily NICU infants.

Why are research dollars being spent on developing a protein that mothers can provide to their own infants?  Why don’t we spend the research dollars refining our techniques on how to best help mothers of premature infants provide their own lactoferrin, provide the best breast pumps, a place to pump, “rooming in” in the NICU and facilitate lots of skin-to-skin holding? In addition, when the mother is supplying her own lactoferrin, she is also colonizing the newborn's GI tract with beneficial bacteria and lowering stress levels in both herself and her infant. 

Liao Y, Jiang R, Lönnerdal B.  Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life. Biochem Cell Biol 2012   90: 476–484.

Lönnerdal B, Jiang R, Du X  Bovine lactoferrin can be taken up by the human intestinal lactoferrin receptor and exert bioactivities. J Pediatr Gastroenterol Nutr 2011 53: 606–614.

Satué-Gracia MT, Frankel E, Rangavajhyala N , German JB.  Lactoferrin in Infant Formulas:  Effect on Oxidation.  J. Agric. Food Chem., 2000, 48:10:4984–4990

Sherman MP, Adamkin DH, Niklas V, Radmacher P, Sherman J, Wertheimer F, Petrak K Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants.  J Pediatr. 2016 Aug; 175:68-73.e3

Sherman MP, Sherman J, Arcinue R, Niklas V.  Randomized Control Trial of Human Recombinant Lactoferrin: A Substudy Reveals Effects on the Fecal Microbiome of Very Low Birth Weight Infants.  J Pediatr. 2016 Jun;173 Suppl:S37-42.

Sherman MP, Pritzl CJ, Xia C, Miller MM, Zaghouani H, Hahm B.  Lactoferrin acts as an adjuvant during influenza vaccination of neonatal mice.  Biochem Biophys Res Commun. 2015 Nov 27;467(4):766-70.

Sherman MP, Miller MM, Sherman J, Niklas V.  Lactoferrin and necrotizing enterocolitis.   Curr Opin Pediatr. 2014 Apr;26(2):146-50.

Sherman MP.  Lactoferrin and necrotizing enterocolitis.  Clin Perinatol. 2013 Mar;40(1):79-91.

Sherman MP, Petrak K. .  Lactoferrin-enhanced anoikis: a defense against neonatal necrotizing enterocolitis.  Med Hypotheses. 2005;65(3):478-82.

Sherman MP, Bennett SH, Hwang FF, Yu C.  Neonatal small bowel epithelia: enhancing anti-bacterial defense with lactoferrin and Lactobacillus GG.  Biometals. 2004 Jun;17(3):285-9.b, c

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