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Zhang Z.,University of Illinois at Urbana - Champaign | Adelman A.S.,Mead Johnson Pediatric Nutrition Institute | Rai D.,Mead Johnson Pediatric Nutrition Institute | Rai D.,DSM Nutritional Products Inc. | And 2 more authors.
Nutrients | Year: 2013

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. © 2013 by the authors; licensee MDPI, Basel, Switzerland.


PubMed | University of Evansville, Urbana University, Mead Johnson Pediatric Nutrition Institute and University of California at Davis
Type: | Journal: Frontiers in nutrition | Year: 2016

Milk oligosaccharides (OSs) are bioactive components known to influence neonatal development. These compounds have specific physiological functions acting as prebiotics, immune system modulators, and enhancing intestine and brain development.The pig is a commonly used model for studying human nutrition, and there is interest in quantifying OS composition of porcine milk across lactation compared with human milk. In this study, we hypothesized that OS and sialic acid (SA) composition of porcine milk would be influenced by stage of lactation.Up to 250mL of milk were collected from seven sows at each of three time points: day 0 (colostrum), days 7-9 (mature), and days 17-19 (weaning). Colostrum was collected within 6h of farrowing and 3-day intervals were used for mature and weaning milk to ensure representative sampling. Milk samples were analyzed for OS profiles by Nano-LC Chip-QTOF MS, OS concentrations via HPAEC-PAD, and SA (total and free) was assessed by enzymatic reaction fluorescence detection.Sixty unique OSs were identified in porcine milk. Neutral OSs were the most abundant at each lactation stage (69-81%), followed by acidic-sialylated OSs (16-29%) and neutral-fucosylated OSs (2-4%). As lactation progressed, acidic OSs decreased (P=0.003), whereas neutral-fucosylated (P<0.001) and neutral OSs (P=0.003) increased throughout lactation. Six OSs were present in all samples analyzed across lactation [lacto-N-difucohexaose I (LNDFH-I), 2-fucosyllactose (2-FL), lacto-N-fucopentaose I (LNFP-I), lacto-N-neohexaose (LNnH), 1-3,-4-d-galactotriose (3-Hex), 3-sialyllactose (3-SL)], while LDFT was present only in colostrum samples. Analysis of individual OS concentrations indicated differences (P=0.023) between days 0 and 7. Conversely, between days 7 and 18, OS concentrations remained stable with only LNnH (P<0.001) and LNDFH-I (P=0.002) decreasing over this period. Analysis of free SA indicated a decrease (P<0.001) as lactation progressed, while bound (P<0.001) and total (P<0.001) SA increased across lactation.Concentrations of OS differ between colostrum and mature milk in the pig, and SA concentrations shift from free to bound forms as lactation progresses. Our results suggest that although porcine milk OS concentration and the number of structures is lower than human milk, the OS profile appears to be closer to human milk rather than to bovine milk, based on previously published profiles.


PubMed | Mead Johnson Pediatric Nutrition Institute, Second Genome, University of Evansville, Georgia Regents University and North Carolina State University
Type: Journal Article | Journal: The Journal of nutrition | Year: 2016

Sialyllactose is a key human milk oligosaccharide and consists of sialic acid (SA) bound to a lactose molecule. Breastfed infants have increased accumulation of ganglioside-bound SA compared with formula-fed infants.This study aimed to determine whether different isomers of sialyllactose enrich brain SA and modulate the microbiome of developing neonatal piglets.Day-old pigs were randomly allocated to 6 diets (control, 2 or 4 g 3-sialyllactose/L, 2 or 4 g 6-sialyllactose/L, or 2 g polydextrose/L + 2 g galacto-oligosaccharides/L; n = 9) and fed 3 times/d for 21 d. Pigs were killed, and the left hemisphere of the brain was dissected into cerebrum, cerebellum, corpus callosum, and hippocampus regions. SA was determined by using a modified periodic acid-resorcinol reaction. Microbial composition of the intestinal digesta was analyzed with the use of 16S ribosomal DNA Illumina sequencing.Dietary sialyllactose did not affect feed intake, growth, or fecal consistency. Ganglioside-bound SA in the corpus callosum of pigs fed 2 g 3-sialyllactose or 6-sialyllactose/L increased by 15% in comparison with control pigs. Similarly, ganglioside-bound SA in the cerebellum of pigs fed 4 g 3-sialyllactose/L increased by 10% in comparison with control pigs. Significant (P < 0.05, Adonis Test) microbiome differences were observed in the proximal and distal colons of piglets fed control compared with 4-g 6-sialyllactose/L formulas. Differences were attributed to an increase in bacterial taxa belonging to species Collinsella aerofaciens (phylum Actinobacteria), genera Ruminococcus and Faecalibacterium (phylum Firmicutes), and genus Prevotella (phylum Bacteroidetes) (Wald test, P < 0.05, DeSeq2) compared with piglets fed the control diet. Taxa belonging to families Enterobacteriaceae and Enterococcaceae (phylum Proteobacteria), as well as taxa belonging to family Lachnospiraceae and order Lactobacillales (phylum Firmicutes), were 2.3- and 4-fold lower, respectively, in 6-sialyllactose-fed piglets than in controls.Supplementation of formula with 3- or 6-sialyllactose can enrich ganglioside SA in the brain and modulate gut-associated microbiota in neonatal pigs. We propose 2 potential routes by which sialyllactose may positively affect the neonate: serving as a source of SA for neurologic development and promoting beneficial microbiota.


Kannampalli P.,Medical College of Wisconsin | Pochiraju S.,Medical College of Wisconsin | Chichlowski M.,Mead Johnson Pediatric Nutrition Institute | Berg B.M.,Mead Johnson Pediatric Nutrition Institute | And 4 more authors.
Neurogastroenterology and Motility | Year: 2014

Background: Increasing evidence indicates a positive effect of probiotics on the nervous system. The objective of this study was to determine if probiotic Lactobacillus rhamnosus GG (LGG) and/or prebiotics polydextrose/galactooligosaccharide (PDX/GOS) can alter the colonic sensitivity in a neonatal rat model of chronic visceral hyperalgesia and to determine whether altered sensitivity is associated with changes in neurotransmitter levels in the brain. Methods: Chronic visceral hyperalgesia was induced in rats by intracolonic administration of zymosan for 3 days during postnatal day 14-16 (P14-P16). After weaning (P21), these pups were divided into groups that received either (1) control diet (CD), (2) PDX/GOS, (3) LGG, or (4) PDX/GOS + LGG. These diets were continued until visceral sensitivity was tested at P60. The viscero-motor response (VMR) to graded colorectal distension (CRD) was determined by measuring the electromyographic (EMG) activity from the abdominal external oblique muscles. The levels of neurotransmitters and biogenic amines were quantified in the frontal cortex, subcortex, brain stem, and cerebellum. Key Results: At P60, the VMR to CRD in the neonatal zymosan-treated rats was significantly higher than neonatal saline-treated rats. In contrast, neonatal zymosan-treated rats that received PDX/GOS or LGG did not exhibit visceral hyperalgesia. The levels of serotonin, noradrenaline, and dopamine were significantly altered in LGG-treated rats compared to other groups. Conclusions & Inferences: Results document that in rats LGG can attenuate neonatally induced chronic visceral pain measured in adulthood. Prolonged intake of LGG alters some key brain neurotransmitters and biogenic amines that could be involved in pain modulation. In rats, Lactobacillus rhamnosus (LGG) can attenuate neonatally induced chronic visceral pain measured in adulthood. Prolonged intake of LGG alters some key brain neurotransmitters and biogenic amines that could be involved in pain modulation. © 2014 John Wiley & Sons Ltd.


PubMed | Afraxis Inc., Psychogenics, Inc. and Mead Johnson Pediatric Nutrition Institute
Type: | Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience | Year: 2016

Early life nutrition plays an important role in brain development. Emerging research in rodents, piglets and humans suggest that prebiotics, milk fat globule membrane and lactoferrin may each play unique roles in brain development and cognitive functions. However, knowledge of their combined impact is lacking. We show here that providing weanling rats with a diet containing milk fat globule membrane, lactoferrin and a polydextrose/galactooligosaccharide prebiotic blend led to a significant increase in total dendritic spine density in hippocampal dentate gyrus neurons. Region-specific alterations in dendritic spine density and morphology could provide a mechanistic basis underlying broader cognitive benefits, but further research is required to demonstrate functional consequences of these observations.


PubMed | Mead Johnson Pediatric Nutrition Institute, TNO, Donders Institute for Brain and Radboud University Nijmegen
Type: | Journal: The Journal of nutritional biochemistry | Year: 2016

Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life.


PubMed | Tytgat Institute for Gastrointestinal and Liver Research and Mead Johnson Pediatric Nutrition Institute
Type: Journal Article | Journal: American journal of physiology. Gastrointestinal and liver physiology | Year: 2016

In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assays. Butyrate (0-20 mM), in contrast to other SCFAs, dose dependently induced aldh1a1 or aldh1a3 transcript expression and increased RA conversion in human and mouse epithelial cells. Epithelial cell line data were replicated in intestinal organoids. In these organoids, butyrate (2-5 mM) upregulated aldh1a3 expression (36-fold over control), whereas aldh1a1 was not significantly affected. Butyrate enhanced maturation markers (Mucin-2 and villin) but did not consistently affect stemness markers or other Wnt target genes (lgr5, olfm4, ascl2, cdkn1). In enteroids, the stimulation of RA production by SCFA was mimicked by inhibitors of histone deacetylase 3 (HDAC3) but not by HDAC1/2 inhibitors nor by agonists of butyrate receptors G-protein-coupled receptor (GPR)43 or GPR109A, indicating that butyrate stimulates RA production via HDAC3 inhibition. We conclude that the SCFA butyrate inhibits HDAC3 and thereby supports epithelial RA production.


PubMed | Mead Johnson Pediatric Nutrition Institute and Federal University of Bahia
Type: | Journal: Nutrition journal | Year: 2016

Nutrients such as docosahexaenoic acid (DHA), prebiotics and -glucan have been associated with reduced incidence of respiratory illnesses and allergic manifestations (AM). Our objective was to assess if consumption of a cows milk-based beverage with these and other nutrients supports respiratory, gastrointestinal, and skin health in otherwise well-nourished, healthy children.In this double-blind, randomized, controlled trial, healthy children (1-4 years of age) from two daycare centers in Brazil were fed three servings/day of a cows milk-based beverage (CMBB; n = 125) containing DHA, the prebiotics polydextrose (PDX) and galactooligosaccharides (GOS), -glucan, and other key nutrients, or a control cows milk-based beverage (control; n = 131) for up to 28 weeks. Occurrence of respiratory infections, diarrheal disease and AM was assessed by study pediatricians and the number of episodes were analyzed with the Cochran-Mantel-Haenszel test and the Andersen-Gill model.The CMBB group had fewer episodes of AM, which included allergic rhinitis or conjunctivitis, wheezing, allergic cough, eczema and urticaria, compared to the control group (p = 0.021). The hazard ratio for increased number of episodes of AM was lower in the CMBB group compared to control (HR, 0.64; 95 % CI 0.47-0.89; p = 0.007). There was no difference in the incidence of respiratory infections and diarrheal disease between groups.A cows milk-based beverage containing DHA, PDX/GOS, and yeast -glucan, and supplemented with micronutrients, including zinc, vitamin A and iron, when consumed 3 times/day for 28 weeks by healthy 1- to 4-year-old children was associated with fewer episodes of allergic manifestations in the skin and the respiratory tract.registration number: NCT01431469.


Woo J.G.,Cincinnati Childrens Hospital Medical Center | Guerrero M.L.,National Institute of Medical science and Nutrition | Ruiz-Palacios G.M.,National Institute of Medical science and Nutrition | Peng Y.-M.,Fudan University | And 6 more authors.
Journal of Nutrition | Year: 2013

Infant feeding practices generally influence infant growth, but it is unclear how introduction of specific foods affects growth across global populations. We studied 3 urban populations in the Global Exploration of Human Milk study to determine the association between infant feeding and anthropometry at 1 y of age. Three hundred sixty-five breastfeeding mother-infant pairs (120 US, 120 China, and 125 Mexico) were recruited soon after the infant's birth. Enrollment required agreement to breastfeed ≥75% for at least 3 mo. Weekly, 24-h, food frequency data were conducted on infants for 1 y and exclusive breastfeeding (EBF) duration and timing of specific complementary food introduction were calculated. Weight and length were measured at age 1 y and anthropometry Z-scores calculated using WHO standards. Cohorts in the 3 urban populations (Shanghai, China; Cincinnati, USA; and Mexico City, Mexico) differed by median EBF duration (5, 14, and 7 wk, respectively; P ≤ 0.001), timing of introduction of meat/eggs/legumes (4.8, 9.3, and 7.0 mo, respectively; P ≤ 0.0001), and other feeding practices. By age 1 y, infants in Shanghai were heavier and longer than Cincinnati and Mexico City infants (P ≤ 0.001). Adjusting for nonfeeding covariates, the only feeding variable associated with anthropometry was EBF duration, which was modestly inversely associated with weight-for-age but not length-for-age or BMI Z-scores at 1 y. Although feeding variables differed by cohort, their impact on anthropometry differences was not consistent among cohorts. Overall, across these urban, international, breast-fed cohorts, differences in specific feeding practices did not explain the significant variation in anthropometry. © 2013 American Society for Nutrition.


PubMed | Wageningen University, Mead Johnson Pediatric Nutrition Institute and University of Cambridge
Type: Journal Article | Journal: Acta paediatrica (Oslo, Norway : 1992) | Year: 2016

Benefits of human breast milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient content. We tested the hypothesis that differential HM total calorie content (TCC) or macronutrient contents may be associated with infancy growth.HM hindmilk samples were collected at ages 4-8 weeks from 614 mothers participating in a representative birth cohort, with repeated infancy anthropometry. HM triglyceride (fat), lipid analytes and lactose (carbohydrate) were measured by (1) H-NMR, and protein content by the Dumas method. TCC and %macronutrients were determined.In 614 HM samples, fat content was as follows: [median(IQR)]: 2.6 (1.7-3.6) g/100 mL, carbohydrate: 8.6 (8.2-8.8) g/100 mL, protein: 1.2 (1.1-1.2) g/100 mL; TCC: 61.8 (53.7-71.3) kcal/100 mL. HM of mothers exclusively breast feeding vs. mixed feeding was more calorific with higher %fat, lower %carbohydrate and lower %protein. Higher HM TCC was associated with lower 12-months body mass index (BMI)/adiposity, and lower 3-12 months gains in weight/BMI. HM %fat was inversely related to 3-12 months gains in weight, BMI and adiposity, whereas %carbohydrate was positively related to these measures. HM %protein was positively related to 12-months BMI.HM analysis showed wide variation in %macronutrients. Although data on milk intakes were unavailable, our findings suggest functional relevance of HM milk composition to infant growth.

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