Bo Lönnerdal

Human Milk K-casein and Inhibition of Helicobacter pylori Adhesion to Human Gastric Mucosa

Summary: Readily digested caseins, which account for almost half of the protein content in human milk, are important as nutritional protein for breast-fed infants. It has also been advocated that part of the antimicrobial activity of human milk resides in the caseins, most likely the glycosylated K-casein. To explore this possibility, we purified K-casein from human milk to homogeneity by a two-step size-exclusion chromatography procedure. Purified human K-casein, in contrast to K-casein purified from bovine milk, effectively inhibited the cell lineage-specific adhesion of fluoroisothiocyanate-labeled Helicobacter pylori to human gastric surface mucous cells. The inhibitory activity was abolished by metaperiodate oxidation and considerably reduced by preincubation with α-L- fucosidase but not with α-N-acetylneuraminidase or endo-β-galactosidase. These results strongly support the view that fucose containing carbohydrate moieties of human K-casein are important for inhibition of H. pylori adhesion and, thus, infection. They also suggest that breastfeeding may protect from infection by H. pylori during early life and that species-specific glycosylation patterns, as illustrated by human and bovine K-casein, partly determine both the narrow host spectrum of this human gastric pathogen and the capacity to resist infection.

Influence of lactoferrin on iron absorption from human milk in infants.

ABSTRACT: Lactoferrin (Lf) is a major iron (Fe)-binding protein in human milk and has been proposed to facilitate Fe absorption. The potential effect of Lf on Fe absorption was investigated by measuring Fe absorption in infants fed breast milk (with its native content of Lf) and the same milk from which Lf had been removed (>97%) by treatment with heparin-Sepharose. Eight breast-fed infants (2–10 mo; mean age 5 mo) were fed 700 to 1000 g of each milk in a randomized, cross-over design with each child acting as his/her own control. The milk was labeled with 8.6 Mmol (0.5 mg) of 58Fe and Fe absorption was measured by quantifying the incorporation of the isotope into red blood cells 14 d after intake using thermal ionization mass spectrometry. Fractional Fe absorption was significantly lower (p < 0.05) from breast milk than from Lf-free breast milk. The geometric mean (range) was 11.8% (3.4–37.4%) for breast milk and 19.8% (8.4–72.8%) for Lf-free breast milk. These results do not support a direct role for Lf in the enhancement of Fe absorption from human milk at this age. In addition, Fe absorption (11.8%) from human milk fed over several feeds was lower than that previously reported for single feed studies.

Sex Differences in Iron Stores of Adolescents: What Is Normal?

We evaluated iron status and its determinants in healthy adolescents. Fasting morning blood samples from a school-based cross-sectional study were analyzed for serum ferritin (SF), serum iron, total iron-binding capacity, and circulating transferrin receptors. Physical development, chronic disease, medication, dietary intake, and physical activity were assessed using clinical examination, questionnaires, and 7-day records. The risk of having low serum ferritin values was estimated using bivariate and multivariate regression. Subjects were 867 healthy Swedish adolescents, 14− and 17-year-olds (472 boys and 395 girls). SF values increased with pubertal stage in boys but not in girls. Five percent of the boys and 15% of the girls had SF values <12 μg/L. Of the 17-year-old boys, 7% compared to 1% of the 17-year-old girls had SF values > 100 μg/L. Forty-one percent of cases with SF values >12 μg/L had serum iron values < 15 μM, and 22% had transferrin saturation values <16%. Mean total iron intakes of the boys were high [1.6 times recommended daily allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low heme iron intakes increased the risk of low iron stores (<12 μg/L) in girls but not in boys. Total iron intake or other dietary factors, physical development, or level of physical activity did not influence the risk of low SF. The findings of this study suggest that the differences in iron status between boys and girls in adolescence results primarily from biological differences other than menstrual bleeding or insufficient iron intake. Furthermore, the results question the role of SF as an indicator of iron deficiency in adolescence, in particular if age and sex are not taken into consideration. We suggest that different reference values for SF, including the cut-off limit for low SF, adjusted for age and sex, should be considered. The high iron intakes and corresponding high SF values found in the older boys are noticeable in light of the possible negative health consequences of iron overload.

Homeostatic Regulation of Iron and Its Role in Normal and Abnormal Iron Status in Infancy and Childhood

Iron is important in neurodevelopment and cognitive function, and globally preventing iron deficiency and iron deficiency anemia remains a high priority. Term breast-fed infants and infants fed an iron-fortified formula usually have a satisfactory iron status during the first 6 months of life, but there are still ambiguities in assessing iron status in infants and how to properly meet their iron requirements. This is particularly evident for preterm infants, who are born with low iron stores, and for whom recommendations for iron provision vary considerably. In part, this may be due to immaturity in the regulation of iron homeostasis in young infants. Whereas 9-month-old infants appear to be able to downregulate iron absorption when being iron replete, 6-month-old infants cannot do this. Iron may be provided as drops or in iron-fortified products, but the forms provided may be metabolized differently, and excess iron in drops may cause adverse effects, possibly due to a limited ability to regulate iron absorption in young infants. Adverse effects are manifested by decreased growth: in well-nourished infants by reduced gain in length, in poorly nourished populations by lower gain in weight. The mechanism behind the decreased growth is not known, but it may involve free radical-mediated effects of iron or an interaction with zinc absorption/homeostasis. It therefore seems that iron drops should not be given to iron-replete infants.