Amino acid profile is a key aspect of human milk (HM) protein quality. We report a systematic review of total amino acid (TAA) and free amino acid (FAA) profiles, in term and preterm HM derived from 13 and 19 countries, respectively. Of the 83 studies that were critically reviewed, 26 studies with 3774 subjects were summarized for TAA profiles, while 22 studies with 4747 subjects were reviewed for FAA. Effects of gestational age, lactation stage, and geographical region were analyzed by Analysis of Variance. Data on total nitrogen (TN) and TAA composition revealed general inter-study consistency, whereas FAA concentrations varied among studies. TN and all TAA declined in the first two months of lactation and then remained relatively unchanged. In contrast, the FAA glutamic acid and glutamine increased, peaked around three to six months, and then declined. Some significant differences were observed for TAA and FAA, based on gestational age and region. Most regional TAA and FAA data were derived from Asia and Europe, while information from Africa was scant. This systematic review represents a useful evaluation of the amino acid composition of human milk, which is valuable for the assessment of protein quality of breast milk substitutes.

We have developed a novel molecular methodology that utilizes stool samples containing intact sloughed epithelial cells to quantify intestinal gene expression profiles in the developing human neonate. Since nutrition exerts a major role in regulating neonatal intestinal development and function, our goal was to identify gene sets (combinations) that are differentially regulated in response to infant feeding. For this purpose, fecal mRNA was isolated from exclusively breast-fed (n = 12) and formula-fed (n = 10) infants at 3 mo of age. Linear discriminant analysis was successfully used to identify the single genes and the two- to three-gene combinations that best distinguish the feeding groups. In addition, putative "master" regulatory genes were identified using coefficient of determination analysis. These results support our premise that mRNA isolated from stool has value in terms of characterizing the epigenetic mechanisms underlying the developmentally regulated transcriptional activation/repression of genes known to modulate gastrointestinal function. As larger data sets become available, this methodology can be extended to validation and, ultimately, identification of the main nutritional components that modulate intestinal maturation and function.

Lactoferrin is the second most abundant whey protein in human milk and is known for its functional benefits, particularly antimicrobial activities. We report a comprehensive evaluation of the published literature on quantitative changes in lactoferrin in term and preterm human milk through the course of lactation. We also considered methods used to quantify lactoferrin. We critically evaluated 94 articles on human milk with 52 meeting study inclusion criteria (2724 women). A descriptive analysis of the data was performed. Lactoferrin concentration was highest during early lactation and rapidly declined to remain relatively unchanged from 1 month to 2 years of lactation. The unweighted mean of mean (±SEM) concentrations of lactoferrin in early milk (<28 days lactation) was 4.91 ± 0.31 g/L (range of means 0.34-17.94 g/L; median 4.03). For mature milk, the mean of means was 2.10 ± 0.87 g/L (range of means 0.44-4.4 g/L; median 1.91). The majority of data were derived from Europe with fewer studies from Africa and South America. There was a paucity of data on preterm milk. This comprehensive dataset explains in detail the longitudinal changes of lactoferrin concentrations in human milk throughout the world and briefly describes factors that may influence these concentrations.

Supplementation of infant formulas with prebiotic ingredients continues the effort to mimic functional properties of human milk. In this double-blind, controlled, 28-day study, healthy term infants received control formula (control group; n ‫؍‬ 25) or control formula supplemented with polydextrose (PDX) and galactooligosaccharide (GOS) (4 g/liter) (PG4 group; n ‫؍‬ 27) or with PDX, GOS, and lactulose (LOS) (either 4 g/liter [PGL4 group; n ‫؍‬ 27] or 8 g/liter [PGL8 group; n ‫؍‬ 25]). A parallel breast-fed group (BF group) (n ‫؍‬ 30) was included. Stool characteristics, formula tolerance, and adverse events were monitored. Fecal bacterial subpopulations were evaluated by culture-based selective enumeration (Enterobacteriaceae), quantitative real-time PCR (Clostridium clusters I, XI, and XIV, Lactobacillus, and Bifidobacterium), and fluorescence in situ hybridization (FISH) (Bifidobacterium). Fecal bacterial community profiles were examined by using 16S rRNA gene PCR-denaturing gradient gel electrophoresis. The daily stool consistency was significantly softer or looser in the BF group than in all of the groups that received formula. The formulas were well tolerated, and the incidences of adverse events did not differ among feeding groups. Few significant changes in bacterial subpopulations were observed at any time point. The bacterial communities were stable; individual profiles tended to cluster by subject rather than by group. Post hoc analysis, however, demonstrated that the bacterial community profiles for subjects in the BF, PG4, PGL4, and PGL8 groups that first received formula at a younger age were less stable than the profiles for subjects in the same groups that received formula at an older age, but there was no difference for the control group. These data indicate that formulas containing PDX, GOS, and LOS blends are more likely to influence gut microbes when administration is begun in early infancy and justify further investigation of the age-related effects of these blends on fecal microbiota.Nondigestible food ingredients called prebiotics pass into the lower gastrointestinal tract and, by definition, may be selectively metabolized by mutualistic microorganisms, such as Lactobacillus spp. and Bifidobacterium spp., which in turn contribute to improved host health (12, 34). After lactose and lipids, oligosaccharides, which have prebiotic activity, are the third largest component of human breast milk (5 to 10 g/liter), and there are as many as 200 distinct molecular structures (5, 26). Lactobacilli and bifidobacteria are the predominant bacteria in the intestinal microbiota of breast-fed infants, whereas infants who receive cow's milk-based infant formulas, which naturally contain low levels of oligosaccharides, often have higher concentrations of potentially pathogenic bacteria, such as Enterobacteriaceae and clostridia, in their intestinal microbiota (4,15,17).Clinical investigations of infant formulas supplemented with galactooligosaccharide (GOS) and fructooligosaccharide (FOS) at a range of concent...

Estrogens regulate multiple activities in breast cancer cells, including proliferation. Whereas these hormones are most commonly known to regulate gene transcription through direct interaction with estrogen receptors (ERs) and with specific DNA sequences of target genes, recent studies show that ER also activates a number of rapid signaling events that are initiated at the cell membrane. To study the membrane-initiated effects of estrogen and separate them from the activities initiated by the nuclear localized ER in human breast cancer cells, we generated MDA-MB-231 breast cancer cell lines that have stably integrated either the wild-type nuclear form of ER (WT-ER) or a modified, membrane-targeted ER (MT-ER) that lacks a nuclear localization sequence and is dually acylated with a myristoylation sequence at the N terminus and a palmitoylation sequence at the C terminus. We demonstrate that MT-ER is membrane localized in the absence of estradiol (E2), showing punctate membrane and cytoplasmic speckles after E2 exposure. In contrast to WT-ER, MT-ER was not down-regulated by E2 or by antiestrogen ICI 182,780 exposure, and MT-ER failed to regulate endogenous E2-responsive genes highly up-regulated by WT-ER. Cells expressing MT-ER showed a greater serum response element-mediated transcriptional response that was partially inhibited by antiestrogen ICI 182,780. The MT-ER and WT-ER differentially altered ERK1/2 and Akt activities and the proliferation of breast cancer cells in response to E2. Hence, this study reveals distinct actions of the MT-ER vs. the WT-ER in effecting estrogen actions in breast cancer cells.

Objective: Understanding nutrient intakes among women of childbearing age within the USA is important given the accumulating evidence that maternal body weight gain and nutrient intakes prior to pregnancy may influence the health and well-being of the offspring. The objective of the present study was to evaluate nutritional status in women of childbearing age and to ascertain the influence of ethnicity and income on nutrient intakes. Design: Nutritional status was assessed using data on nutrient intakes through foods and supplements from the National Health and Nutrition Examination Survey. Biomarker data from the Centers for Disease Control and Prevention were used to assess nutritional status for selected nutrients. Poverty-income ratio was used to assess family income. Subjects: White (n 1560), African-American (n 889) and Mexican-American (n 761) women aged 19-30 and 31-50 years were included. Setting: A nationally representative sample of non-pregnant women of childbearing age resident in the USA. Results: African-American women had the lowest intakes of fibre, folate, riboflavin, P, K, Ca and Mg. Women (31-50 years) with a poverty-income ratio of ≤1·85 had significantly lower intakes of almost all nutrients analysed. Irrespective of ethnicity and income, a significant percentage of women were not consuming the estimated recommended amounts (Estimated Average Requirement) of several key nutrients: vitamin A (~80 %), vitamin D (~78 %) and fibre (~92 %). Nutrient biomarker data were generally reflective of nutrient intake patterns among the different ethnic groups. Conclusions: Women of childbearing age in the USA are not meeting nutrient intake guidelines, with differences between ethnic groups and socio-economic strata. These factors should be considered when establishing nutrition science advocacy and policy.

PDX and GOS added to formula do not induce BT in healthy piglets. Low levels of bacteria in MLN of healthy neonatal piglets may reflect mucosal sampling rather than pathological BT.

Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.