Molecular Forms of Lactoferrin in Stool and Urine from Infants Fed Human Milk

Abstract

ABSTRACT. The molecular forms of lactoferrin (LF) were of the infant (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Recent studies demonstrate that the urinary examined in stools and urine collected at 2.5 or 5 wk of excretion of IgA (1 1, 12), total secretory component (12), and age from very low birth wt infants fed either a cow's milk LF (12) was greater in human milk as compared to cow's milkformula or a fortified human milk preparation. LF was not fed infants. Those findings were particularly germane because found by Western blotting in excreta from infants fed cow's urine is a secretion whose formation is far removed from direct milk. In contrast, intact and fragmented forms of I F were contact with ingested human milk. In one report (12), prelimidetected in stools and concentrated urine of each infant nary evidence was presented that several fragments, as well as who received human milk. Only intact LF was detected in intact LF, were excreted in the urine of VLBW infants who were the fortified human milk preparation, whereas many types fed human milk. In this investigation, we sought to ascertain of LF fragments were present in the stools and urine. The whether these molecular fragments of LF in the urine of those approximate molecular wt of the most prominent fragments VLBW infants originated in the gastrointestinal tract. Therefore, were 44, 38, 34, and 32 kD. However, the stools also we examined stools as well as urine for these fragments from displayed lower molecular wt fragments that were not VLBW infants fed human milk. In addition, we attempted to found in urines of those infants. The LF fragments in those determine whether the fragments may contribute to the quantiexcreta were similar in size to those produced in vitro by tative measurement of LF in those excreta, and whether the limited digestion of apo-LF with trypsin. Furthermore, fragments are created by the action of certain enzymes found in fragments produced by in vitro proteolysis were immuno-the digestive tract. reactive in an ELISA for LF. Thus, the fragments of LF in stools of very low birth wt infants fed human milk appeared to be produced by in vivo proteolysis, and the MATERIALS AND METHODSclose resemblance between the LF fragments in the stools and urine suggests that the urinary LF fragments origiStudy design.The study was approved by the institutional nated in the gastrointestinal tract. It remains unclear, review boards of both institutions. Two groups of VLBW infants however, whether the whole LF molecules that were frag-from the same hospital population were investigated (12, 13). mented were derived solely from ingested LF in human One infant received CMF (Similac PM 60140 or Similac 24, milk or in part from LF produced by the infant in response Ross Laboratories, Columbus, OH) and the second received to human milk feedings.

Origin of Intact Lactoferrin and Its DNA-Binding Fragments Found in the Urine of Human Milk-Fed Preterm Infants. Evaluation by Stable Isotopic Enrichment

“…The origin, nature, and regulation of the lactoferrin cleavage event(s) are not known. The indicated fragments were not detected in the milk of these mothers, in the milk of 10 other mothers that we studied (unpublished observations), or of others studied previously (21). These lactofemn fragments that bind to DNA also are not detected in the milk of other mammals (bovine and porcine) we have studied (unpublished observations).…”

“…Fecal excretion, however, accounts for only a few percent (1-6%) of the lactofemn fed ( 16,17), and most fecal lactofemn is degraded to lower molecular mass forms (1 9-2 1). Investigators have also reported higher levels of lactofenin and lactoferrin fragments, free secretory component, and secretory IgA in the urine of infants fed human milk than in the urine of infants fed a bovine milk-based formula (21,22). The molecular sizes of these immune factors are larger than normally filtered by glomeruli (23).…”

Human Lactoferrin and Peptides Derived from a Surface-Exposed Helical Region Reduce ExperimentalEscherichia coliUrinary Tract Infection in Mice

“…The reduction of UTI by breast-feeding has been attributed to the content in milk of secretory immunoglobulin A antibodies and oligosaccharides, which inhibit the adherence of enterobacteria to the uroepithelial cells (6,34). However, milk contains several other, potentially protective factors (e.g., lactoferrin [LF], lysozyme, and complement factors) which could play a role in UTI, especially since intact human LF (hLF) and fragments thereof have been found in the urine of infants fed human milk (11,16). In addition, two forms of LF (one intact and one ''nicked'') of maternal origin have been isolated from the urine of preterm infants fed human milk (17).…”

Killing the Messenger in the Nick of Time: Persistence of Breast Milk sCD14 in the Neonatal Gastrointestinal Tract

“…However, these immunologically important molecules would have to remain intact and active throughout the gastrointestinal tract to provide immune benefits for the newborn. SIgA (5,6) and lactoferrin (7,8), for example, have been shown to survive the passage through the infant digestive system, with observed fecal excretion rates of 160 mg/d and 14.3 mg/d, respectively (6).…”