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In a previous study, we reported that human milk oligosaccharides (HMOs) isolated from five donor milk samples possessed antimicrobial and antibiofilm activity against Streptococcus agalactiae, also known as Group B Streptococcus or GBS. Herein, we present a broader evaluation of the antimicrobial and antibiofilm activity by screening HMOs from 14 new donors against three strains of GBS and two of the ESKAPE pathogens of particular interest to child health, Staphylococcus aureus and Acinetobacter baumannii. Growth and biofilm assays showed that HMOs from these new donors possessed antimicrobial and antibiofilm activity against all three strains of GBS, antibiofilm activity against methicillin-resistant S. aureus strain USA300, and antimicrobial activity against A. baumannii strain ATCC 19606.
Human milk contains many bioactive components, including secretory IgA, oligosaccharides, and milk-associated proteins. We assessed the antiviral effects of several components of milk against mammalian reoviruses. We found that glucocerebroside (GCB) inhibited the infectivity of reovirus strain type 1 Lang (T1L), whereas gangliosides GD3 and GM3 and 3'-sialyllactose (3SL) inhibited the infectivity of reovirus strain type 3 Dearing (T3D). Agglutination of erythrocytes mediated by T1L and T3D was inhibited by GD3, GM3, and bovine lactoferrin. Additionally, α-sialic acid, 3SL, 6'-sialyllactose, sialic acid, human lactoferrin, osteopontin, and α-lactalbumin inhibited hemagglutination mediated by T3D. Using single-gene reassortant viruses, we found that serotype-specific differences segregate with the gene encoding the viral attachment protein. Furthermore, GD3, GM3, and 3SL inhibit T3D infectivity by blocking binding to host cells, whereas GCB inhibits T1L infectivity post-attachment. These results enhance an understanding of reovirus cell attachment and define a mechanism for the antimicrobial activity of human milk.
Copyright © 2012 Elsevier Inc. All rights reserved.
Industrially produced trans-fatty acids (TFAs) consumed in Western diets are incorporated into maternal and fetal tissues and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared with unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis, we fed female C57/BL6 mice identical Western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition, and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography) and glucose metabolism were assessed at weaning and adulthood. Trans-fatty acid exposure through breast milk caused significant early growth retardation (P < .001) and higher fasting glucose (P = .01), but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (P = .02) may contribute to later catch-up growth and leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (P < .05) and greater abdominal fat (P = .01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. Trans-fatty acid surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism.
Copyright 2010 Elsevier Inc. All rights reserved.
Four pregnancies in a women with moderately severe deficiency of methionine adenosyltransferase I/III (MAT I/III) activity are reported. She is an apparent homozygote for a point mutation in MAT1A, the gene that encodes the catalytically active subunit of MAT I/III. This mutation reduces the activity of her expressed enzyme to some 11% of wild-type. She was the first such individual identified in the United States, and these are the first pregnancies known in anyone with this extent of MAT I/III deficiency. No adverse effects were noted in the mother. Three normal babies resulted, but fetal arrest was detected in one embryo at 10-11 weeks gestation. Plasma methionine concentrations remained virtually constant at their elevated levels of 300-350 micromol/L throughout the pregnancies. Plasma free choline was below the reference range. In view of the evidence that maternal choline delivery to the fetus is important for brain development, it was suggested the patient ingest two eggs daily from gestation week 17. Plasma choline and phosphatidylcholine tended to rise during such supplementation. Plasma cystathionine concentrations rose progressively to far above normal during these pregnancies, but not during pregnancies in control women. This may be explained by delivery of excessive methionine to the fetus, with consequent increased cystathionine synthesis by fetal tissues. Because fetal tissues lack gamma-cystathionase, presumably cystathionine accumulated abnormally in the fetus and was transferred in abnormal amounts back to the mother. Plasma and urinary concentrations of methionine transamination metabolites rose during pregnancy for reasons that remain obscure.
A study was conducted to (1) determine the concentration of DDT/DDE in the breast milk of mothers residing in the Yakima river basin (WA, USA), (2) assess the relative impact of fish consumption on the total DDT/DDE body burden, and (3) determine if the amount of DDT/DDE received by their breastfed infants exceeds levels that could produce deleterious effects. Results indicate that fish consumption did not significantly increase DDT/DDE breast milk concentrations. Subjects born in Mexico had elevated levels of DDT/DDE in breast milk compared to levels found in US born subjects regardless of fish consumption. Infant daily intake levels for the various subject groups were determined and compared to acceptable and tolerable daily intake levels. With benefits of breast milk well understood, breastfeeding should still be strongly recommended for these mothers.
The fractional synthesis rate (FSR) of cholesterol was measured in 6 breast-fed and 12 formula-fed infants (ages 4 to 5 months) using the 2H2O method. The breast-fed infants had higher cholesterol intakes (18.2 +/- 4.0 vs. 3.4 +/- 1.8 mg/kg per day, P = 0.001), plasma total cholesterol (183 +/- 47 vs. 112 +/- 22 mg/dl, P = 0.013), and plasma low density lipoprotein (LDL)-cholesterol (83 +/- 26 vs. 48 +/- 16 mg/day, P = 0.023) than the formula-fed infants (6.9 +/- 2.6 vs. 2.1 +/- 0.6%/day, P < 0.001). Among all infants, there was a significant inverse relationship (P = 0.002, r = 0.66) between the FSR of cholesterol and dietary cholesterol intake. Our findings indicate that the greater cholesterol intake of the breast-fed infants was associated with elevated plasma LDL-cholesterol concentrations and that cholesterol synthesis in human infants may be efficiently regulated via HMG-CoA reductase when infants are challenged with high intakes of dietary cholesterol.
Nutrient effects on cholesterol fractional synthesis rates (FSR) in infancy by stable isotope determination have not been studied. We hypothesized that FSR is significantly reduced with high dietary cholesterol and phytoestrogen intake and increased with low dietary cholesterol and phytoestrogen intake. We prospectively studied 33 term male infants exclusively fed human milk (high cholesterol, low phytoestrogen, n = 12), cow milk-based formula (low cholesterol, low phytoestrogen, n = 8), soy milk-based formula (zero cholesterol, high phytoestrogen, n = 7), or soy milk-based formula modified to contain cholesterol (low cholesterol, high phytoestrogen, n = 6) during the first 4 mo of life. Cholesterol FSR was determined from rate of incorporation of deuterium into erythrocyte membrane cholesterol, and urinary isoflavone excretion (an index of dietary phytoestrogen exposure) was measured by gas chromatography-mass spectrometry. Significant differences in cholesterol FSR were found. FSR (%/d) was lowest in human milk (2.62 +/- 0.38), highest in soy milk-based formula (9.40 +/- 0.51), and intermediate in cow milk-based and modified soy milk-based formula (6.90 +/- 0.48 and 8.03 +/- 0.28, respectively), p < 0.0001. Cholesterol FSR was significantly lower in modified soy milk-based compared with soy milk-based formula, p < 0.05. We also show for the first time that dietary phytoestrogens are absorbed and excreted by the infant fed soy protein-based formula. Urinary isoflavone excretion was inversely related to cholesterol FSR, but it was not significantly related to serum cholesterol concentration. We conclude that the type of infant nutrition and dietary cholesterol are major factors influencing cholesterol fractional synthesis rates in infancy.
The partitioning of dietary and endogenous nutrients during lactation is not well understood. To examine associations between plasma hormone and substrate profiles and indices of either maternal body protein metabolism or lactational performance, we measured plasma insulin, cortisol, prolactin, thyroxine, triiodothyronine, individual amino acid, blood urea nitrogen, and prealbumin concentrations in lactating and nulliparous women in the postabsorptive state. We related these measurements to the subjects' nitrogen balance, urinary 3-methylhistidine excretion, [1-13C]leucine metabolism and milk production. Insulin concentrations showed significant positive relationships with nitrogen balance and prealbumin concentrations; cortisol levels showed a significant negative relationship with nitrogen balance and a significant positive relationship with leucine incorporation into protein. Thyroid hormone concentrations showed significant positive relationships with urinary 3-methylhistidine excretion, leucine incorporation into protein, and milk production. Proline concentrations were associated positively with nitrogen balance and negatively with leucine incorporation into protein, whereas glutamate-glutamine concentrations showed positive associations with leucine oxidation and milk nitrogen concentrations. We propose that insulin and cortisol modulate the channeling of nutrients between anabolic and anti-anabolic aspects of maternal body protein metabolism, whereas thyroid hormones and cortisol modulate nutrient partitioning toward milk production and visceral protein synthesis. We suggest that some nonessential amino acids (proline, glutamate-glutamine) may become limiting during lactation because of their unique contributions to milk protein synthesis.
Infants with neonatal alloimmune thrombocytopenia are at risk of severe intracranial haemorrhage. Placental transfer of maternal immunoglobulin G (IgG) directed against fetal platelet antigens is known to be the underlying mechanism. Since breast milk contains IgG it is theoretically possible that breast feeding of these infants could cause thrombocytopenia. The following case report shows that an infant with neonatal alloimmune thrombocytopenia may be safely breast fed, even when the breast milk contains the platelet specific antibody (HPA-1a).