ABSTRACT
Dental caries are a major public health problem worldwide. The aim of this study was to compare the effects of children's follow-on instant powdered cow's milk formula, buffalo milk formula and a chicken-based formula on microhardness of bovine enamel with artificial caries-like lesions. Forty bovine teeth were each placed in acrylic blocks and the enamel surfaces were polished to create flat 5 x 5 millimeter surfaces. The teeth surfaces were then demineralized using 0.1M lactic acid (pH 4.5) to achieve an enamel microhardness of 35-65 Vickers Hardness Numbers (VHN). All specimens were then randomly allocated into one of 4 groups (n=10/group). For remineralization, each group was soaked in a different kind of milk formula for 2 hours at 37°C except group 1 which was a negative control (artificial saliva) group. Group 2 was soaked in Murrah™ buffalo milk formula (a positive control ), group 3 in S-26-Promil-Gold™ (cow's milk formula) and group 4 in a chicken-based formula (Siriraj Hospital, Mahidol University). The microhardness of the specimens was then measured again. Data were analyzed using a one-way ANOVA and paired t-test with a 95% confidence interval. After exposure to the formula, the mean VHN for each study group was significantly higher (paired t-test, p < 0.05) except for group 1 (p = 0.345). The mean VHN for the the Murrah™ buffalo milk formula, the chicken-based formula and the S-26-Promil-Gold™ formula group were not significantly different from each other (one-way ANOVA, p > 0.05). In conclusion, S-26-Promil-Gold™ follow-on cow milk formula, Murrah™ buffalo milk formula and the chicken-based formula all increased bovine enamel microhardness after soaking for 2 hours.
Subject(s)
Dental Enamel/drug effects , Hardness/drug effects , Infant Formula/pharmacology , Animals , Buffaloes , Cattle , Chickens , Dental Caries/epidemiology , Humans , In Vitro Techniques , Infant , Infant Formula/chemistry , Poverty , Random Allocation , Saliva, Artificial/pharmacology , Thailand/epidemiology , Tooth RemineralizationABSTRACT
UNLABELLED: Effects of the dietary glycaemic load on postprandial blood glucose and insulin response might be of importance for fat deposition and risk of obesity. We aimed to investigate the metabolic effects, acceptance and tolerance of a follow-on formula containing the low glycaemic and low insulinaemic carbohydrate isomaltulose replacing high glycaemic maltodextrin. Healthy term infants aged 4 to 8 completed months (n = 50) were randomized to receive the intervention follow-on formula (IF, 2.1g isomaltulose (Palatinose™)/100mL) or an isocaloric conventional formula (CF) providing 2.1g maltodextrin/100mL for four weeks. Plasma insulinaemia 60 min after start of feeding (primary outcome) was not statistically different, while glycaemia adjusted for age and time for drinking/volume of meal 60 min after start of feeding was 122(105,140) mg/dL in IF (median, interquartile range) and 111(100,123) in CF (p = 0.01). Urinary c-peptide:creatinine ratio did not differ (IF:81.5(44.7, 96.0) vs. CF:56.8(37.5, 129),p = 0.43). Urinary c-peptide:creatinine ratio was correlated total intake of energy (R = 0.31,p = 0.045), protein (R = 0.42,p = 0.006) and fat (R = 0.40,p = 0.01) but not with carbohydrate intake (R = 0.22,p = 0.16). Both formulae were well accepted without differences in time of crying, flatulence, stool characteristics and the occurrence of adverse events. The expected lower postprandial plasma insulin and blood glucose level due to replacement of high glycaemic maltodextrin by low glycaemic isomaltulose were not observed in the single time-point blood analysis. In infants aged 4 to 8 completed months fed a liquid formula, peak blood glucose might be reached earlier than 60 min after start of feeding. Non-invasive urinary c-peptide measurements may be a suitable marker of nutritional intake during the previous four days in infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01627015.
Subject(s)
Child Development/drug effects , Infant Formula/pharmacology , Isomaltose/analogs & derivatives , Blood Glucose/drug effects , C-Peptide/urine , Creatinine/urine , Double-Blind Method , Energy Intake/drug effects , Female , Glycemic Load/drug effects , Humans , Infant , Insulin/blood , Isomaltose/pharmacology , Male , Polysaccharides/pharmacologyABSTRACT
BACKGROUND: Breastfeeding is associated with a variety of positive health outcomes in children and is recommended exclusively for the first 6 months of life; however, 50-70 % of infants in the US are formula-fed. To test the hypothesis that immune system development and function in neonates and infants are significantly influenced by diet, 2-day old piglets were fed soy or milk formula (n = 6/group/gender) until day 21 and compared to a sow-fed group (n = 6/gender). METHODS: Histomorphometric analyses of ileum, jejunum and Peyer's patches were carried out, to determine the inflammation status, mRNA and protein expression of pro-inflammatory, anti-inflammatory and growth-related chemokines and cytokines. RESULTS: In formula-fed animals, increases in ileum and jejunum villus height and crypt depth were observed in comparison to sow-fed animals (jejunum, p < 0.01 villus height, p < 0.04 crypt depth; ileum p < 0.001 villus height, p < 0.002 crypt depth). In formula-fed the lymphoid follicle size (p < 0.01) and germinal centers (p < 0.01) with in the Peyer's patch were significantly decreased in comparison to sow-fed, indicating less immune education. In ileum, formula diet induced significant up-regulation of AMCFII, IL-8, IL-15, VEGFA, LIF, FASL, CXCL11, CCL4, CCL25 and down-regulation of IL-6, IL-9, IL-10, IL-27, IFNA4, CSF3, LOC100152038, and LOC100736831 at the transcript level. We have confirmed some of the mRNA data by measuring protein, and significant down-regulation of anti-inflammatory molecule IL-10 in comparison to sow-fed piglets was observed. To further determine the membrane protein expression in the ileum, VE-cadherin, occludin, and claudin-3, Western blot analyses were conducted. Sow fed piglets showed significantly more VE-Cadherin, which associated with levels of calcium, and putrescine measured. It is possible that differences in GI tract and immune development are related to shifts in the microbiome; notably, there were 5-fold higher amounts of Lactobacillaceae spp and 3 fold higher Clostridia spp in the sow fed group in comparison to milk formula-fed piglets, whereas in milk formula-fed pigs Enterobacteriaceae spp was 5-fold higher. CONCLUSION: In conclusion, formula diet alters GI morphology, microbial abundance, intestinal barrier protein VE-cadherin and anti-inflammatory molecule IL-10 expression. Further characterization of formula effects could lead to modification of infant formula to improve immune function, reduce inflammation and prevent conditions such as allergies and infections.
Subject(s)
Antigens, CD/genetics , Cadherins/genetics , Cytokines/drug effects , Gastrointestinal Microbiome/drug effects , Infant Formula/pharmacology , Intestine, Small/drug effects , Milk , RNA, Messenger/drug effects , Soy Foods , Animals , Animals, Newborn , Antigens, CD/metabolism , Cadherins/metabolism , Calcium/metabolism , Cytokines/genetics , Cytokines/metabolism , Diet , Down-Regulation , Fas Ligand Protein/drug effects , Fas Ligand Protein/genetics , Fas Ligand Protein/metabolism , Humans , Ileum/drug effects , Ileum/metabolism , Ileum/microbiology , Ileum/pathology , Infant, Newborn , Interferon-alpha/drug effects , Interferon-alpha/genetics , Interferon-alpha/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , Interleukin-15/genetics , Interleukin-15/metabolism , Interleukin-27/genetics , Interleukin-27/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-8/drug effects , Interleukin-8/genetics , Interleukin-8/metabolism , Interleukin-9/genetics , Interleukin-9/metabolism , Intestine, Small/metabolism , Intestine, Small/microbiology , Intestine, Small/pathology , Jejunum/drug effects , Jejunum/metabolism , Jejunum/microbiology , Jejunum/pathology , Leukemia Inhibitory Factor/drug effects , Leukemia Inhibitory Factor/genetics , Leukemia Inhibitory Factor/metabolism , Peyer's Patches/drug effects , Peyer's Patches/immunology , RNA, Messenger/metabolism , Swine , Up-Regulation , Vascular Endothelial Growth Factor A/drug effectsABSTRACT
l-Fucose is a natural monosaccharide present in mammals where it is found predominantly as an O-glycosidically linked component of glycoproteins, glycolipids, and oligosaccharides. It is also present in its free form in human breast milk (human milk monosaccharide). l-Fucose plays important roles in the development of the immune and nervous systems and is involved in cognitive function and memory formation. The human-identical milk monosaccharide l-fucose is therefore proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of l-fucose, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. l-Fucose was without maternal toxicity or compound-related adverse effects on female reproduction and general growth and development of offspring at a maternal dietary level up to 1%, equivalent to a dose of 1655 mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 1% (highest level tested), corresponding to doses of 516 and 665 mg/kg bw/day in males and females, respectively. l-Fucose was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of l-fucose in infant formula and as a food ingredient at levels equivalent to those present in human breast milk.
Subject(s)
Fucose/administration & dosage , Infant Formula/pharmacology , Milk, Human/metabolism , Monosaccharides/adverse effects , Animals , Female , Humans , Infant , Male , Mutagenicity Tests/methods , Rats , Rats, Sprague-Dawley , Reproduction/drug effects , SafetySubject(s)
Animals , Female , Male , Animal Feed , Animals, Newborn/metabolism , Arachidonic Acid/biosynthesis , Docosahexaenoic Acids/metabolism , Gestational Age , Infant Formula/pharmacology , Papio/physiology , Body Weight , Brain/metabolism , Erythrocytes/metabolism , Linear Models , Liver/metabolism , Organ Size , Time FactorsABSTRACT
AIMS: To evaluate the impact of oligofructose (OF)-supplemented infant formula on fecal microbiota, stool characteristics, and hydration. METHODS: Ninety-five formula-fed infants were randomized to α-lactalbumin-enriched control formula (CF) or identical formula with 3.0 g/L OF (EF) for 8 weeks; 50 infants fed human milk (HM) were included. RESULTS: Eighty-four infants completed the study, 70 met per-protocol criteria. Over 8 weeks, bifidobacteria increased more in EF than CF group (0.70 vs. 0.16 log10 bacterial counts/g dry feces, P = .008); EF was not significantly different from HM group (P = .32). EF group stool consistency was intermediate between CF and HM groups; at week 8, EF group had softer stools than CF (5-point scale: 1 = hard, 5 = watery; consistency score 3.46 vs. 2.82, P = .015) without significant differences in stool frequency. Physician-assessed hydration status was normal for all infants. CONCLUSIONS: Infant formula with 3.0 g/L OF promoted bifidobacteria growth and softer stools without adversely affecting stool frequency or hydration.
Subject(s)
Feces/microbiology , Food, Fortified , Infant Formula/pharmacology , Lactalbumin/pharmacology , Microbiota/drug effects , Oligosaccharides/pharmacology , Body Water/drug effects , Double-Blind Method , Female , Humans , Infant, Newborn , Lactalbumin/urine , Male , Oligosaccharides/urine , Prospective StudiesABSTRACT
Human milk is the gold standard for nourishment of early infants because it contains a number of bioactive components, such as human milk oligosaccharides (HMOs). The high concentration and structural diversity of HMOs are unique to humans. HMOs are a group of complex and diverse glycans that are resistant to gastrointestinal digestion and reach the infant colon as the first prebiotics. N-acetyl-glucosamine containing oligosaccharides were first identified 50 years ago as the 'bifidus factor', a selective growth substrate for intestinal bifidobacteria, thus providing a conceptual basis for HMO-specific bifidogenic activity. Bifidobacterial species are the main utilisers of HMOs in the gastrointestinal tract and represent the dominant microbiota of breast-fed infants, and they may play an important role in maintaining the general health of newborn children. Oligosaccharides are also known to directly interact with the surface of pathogenic bacteria, and various oligosaccharides in milk are believed to inhibit the binding of pathogens and toxins to host cell receptors. Furthermore, HMOs are thought to contribute to the development of infant intestine and brain. Oligosaccharides currently added to infant formula are structurally different from the oligosaccharides naturally occurring in human milk and, therefore, they are unlikely to mimic some of the structure-specific effects. In this review, we describe how HMOs can modulate gut microbiota. This article summarises information up to date about the relationship between the intestinal microbiota and HMOs, and other possible indirect effects of HMOs on intestinal environment.
Subject(s)
Anti-Infective Agents/pharmacology , Intestines/microbiology , Microbiota/drug effects , Milk, Human , Oligosaccharides/pharmacology , Acetylglucosamine/pharmacology , Bifidobacterium , Brain/growth & development , Humans , Infant , Infant Formula/pharmacology , Infant, Newborn , N-Acetylneuraminic Acid/pharmacology , PrebioticsABSTRACT
Relatively high amounts of protein are required to achieve normal fractional protein synthetic rates during the late second through early third trimester of fetal growth. Once preterm infants achieve higher protein intakes for sustained periods, growth begins to approximate that of the normally growing fetus and long-term neurodevelopmental outcomes are improved. Preterm formulas have been developed that are enriched in protein. This review discusses several factors when using standard preterm formulas and high-protein preterm formulas in the neonatal intensive care unit, with an emphasis on quantity and quality of enteral protein delivery and risks to insufficient and/or excess protein administration.
Subject(s)
Enteral Nutrition/methods , Infant Formula/pharmacology , Infant Nutritional Physiological Phenomena/physiology , Infant, Premature/growth & development , Humans , Infant, Newborn , Intensive Care Units, NeonatalABSTRACT
The rapid expansion of commercially available fermented food products raises important safety issues particularly when infant food is concerned. In many cases, the activity of the microorganisms used for fermentation as well as what will be the immunological outcome of fermented food intake is not known. In this manuscript we used complex in vitro, ex-vivo and in vivo systems to study the immunomodulatory properties of probiotic-fermented products (culture supernatant and fermented milk without live bacteria to be used in infant formula). We found in vitro and ex-vivo that fermented products of Lactobacillus paracasei CBA L74 act via the inhibition of proinflammatory cytokine release leaving anti-inflammatory cytokines either unaffected or even increased in response to Salmonella typhimurium. These activities are not dependent on the inactivated bacteria but to metabolic products released during the fermentation process. We also show that our in vitro systems are predictive of an in vivo efficacy by the fermented products. Indeed CBA L74 fermented products (both culture medium and fermented milk) could protect against colitis and against an enteric pathogen infection (Salmonella typhimurium). Hence we found that fermented products can act via the inhibition of immune cell inflammation and can protect the host from pathobionts and enteric pathogens. These results open new perspectives in infant nutrition and suggest that L. paracasei CBA L74 fermented formula can provide immune benefits to formula-fed infants, without carrying live bacteria that may be potentially dangerous to an immature infant immune system.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Colitis/prevention & control , Dendritic Cells/metabolism , Fermentation/drug effects , Infant Formula/pharmacology , Lactobacillus/metabolism , Milk/metabolism , Salmonella typhimurium/drug effects , Administration, Oral , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Colitis/drug therapy , Colitis/microbiology , Dendritic Cells/drug effects , Humans , Infant , Infant Formula/administration & dosage , Inflammation Mediators/metabolism , Mice , Mice, Inbred C57BL , Protective Agents/administration & dosage , Protective Agents/pharmacology , Protective Agents/therapeutic use , Salmonella Infections, Animal/microbiology , Salmonella Infections, Animal/prevention & control , Salmonella typhimurium/physiologyABSTRACT
BACKGROUND: Effects of palm olein (POL) on calcium and fat metabolic balance and gastrointestinal (GI) tolerance have been clinically evaluated but its use in combination with palm kernel oil (PKO), and canola oil has not been similarly assessed in infants. METHODS: Calcium and fat balance and GI tolerance were evaluated in 33 healthy term infants (age = 68-159 d) in a randomized, double-blinded, 14 d crossover trial at a day care center in Salvador, Brazil; followed by a 4d hospital ward metabolic balance study in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; one containing POL (44% of total fat), PKO (21.7%) and canola oil (18.5%) as predominant fats (PALM), and the other containing none (NoPALM). Occasional human milk (HM) supplementation was allowed at home. RESULTS: Formula and HM intakes, and growth were not different (p > 0.05). Calcium absorption (%) for infants fed NoPALM (58.8 ± 16.7%; means ± SD) was higher (p = 0.023) than those fed PALM (42.1 ± 19.2%), but was not significant (p = 0.104) when calcium intake was used as a covariate. Calcium intake was higher (p < 0.001) in NoPALM versus PALM fed infants. However, calcium retention (%) was higher in infants fed NoPALM compared to PALM with (p = 0.024) or without (p = 0.015) calcium intake as a covariate. Fat absorption (%) for NoPALM was greater than PALM fed infants (NoPALM = 96.9 ± 1.2 > PALM = 95.1 ± 1.5; p = 0.020 in Study Period I). Mean rank stool consistency was softer in infants fed NoPALM versus PALM (p < 0.001; metabolic period). Adverse events, spit-up/vomit, fussiness and gassiness were not different (p > 0.05). Formula acceptability was high and comparable for both formula feedings, regardless of HM supplementation. CONCLUSIONS: Term infants fed PALM based formula (containing palm olein, palm kernel and canola oils) demonstrated lower calcium retention and fat absorption, and less softer stool consistency versus infants fed NoPALM based formula. Study suggested formula fat differences may affect GI function in infants.
Subject(s)
Arecaceae/chemistry , Calcium/metabolism , Dietary Fats, Unsaturated/pharmacology , Dietary Fats/pharmacology , Dyspepsia/chemically induced , Infant Formula/pharmacology , Lipid Metabolism/drug effects , Plant Oils/pharmacology , Calcium, Dietary/pharmacokinetics , Chemical Fractionation , Cross-Over Studies , Dietary Fats/administration & dosage , Dietary Fats/adverse effects , Dietary Fats, Unsaturated/administration & dosage , Double-Blind Method , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Monounsaturated/pharmacology , Female , Humans , Infant , Infant Formula/chemistry , Intestinal Absorption , Male , Milk, Human , Palm Oil , Plant Extracts/chemistry , Plant Oils/administration & dosage , Plant Oils/adverse effects , Plant Oils/chemistry , Rapeseed Oil , Seeds/chemistry , SolubilityABSTRACT
INTRODUCTION: The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC). MATERIAL AND METHODS: Newborn Sprague-Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression. RESULTS: The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p<0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1. DISCUSSION: Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.
Subject(s)
Cyclooxygenase 2/biosynthesis , Enterocolitis, Necrotizing/metabolism , Infant Formula/pharmacology , Interleukin-6/biosynthesis , Interleukin-8/biosynthesis , Intestinal Mucosa/metabolism , Animals , Animals, Newborn , Body Weight , Cyclooxygenase 2/genetics , Disease Models, Animal , Enterocolitis, Necrotizing/surgery , Humans , Ileum/metabolism , Infant , Inflammation , Interleukin-6/genetics , Interleukin-8/genetics , Milk , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Time FactorsABSTRACT
BACKGROUND: Natural killer (NK) cells are components of the innate immune defense system, and their levels differ between breast and formula-fed (FF) infants. Lactoferrin (Lf) modulates NK cell cytotoxicity ex vivo. We hypothesized that dietary bovine Lf (bLf) would increase NK cell populations and cytotoxicity. METHODS: Piglets were sow-reared (SR), FF, or 1 g/l bLf-fed (LF) for 21 d. NK cells (CD3(-)CD4(-)CD8(+)) in blood (peripheral blood mononuclear cells (PBMCs)), spleen, and mesenteric lymph node (MLN) were determined by flow cytometry. PBMC NK cells were tested for cytotoxic activity against target K562 cells ex vivo in the presence of media (unstimulated), interleukin-2, or bLf. NK cell mRNA expression was determined by reverse transcription-quantitative PCR. RESULTS: SR and LF piglets had more NK cells in MLN (P = 0.0097) and spleen (P = 0.0980) than FF piglets. In PBMCs, SR piglets had more NK cells than FF piglets (P = 0.0072); LF piglets were intermediate and not different from FF or SR piglets. NK cell intelectin-2 mRNA expression was 2.5-fold higher (P = 0.0095) in LF than SR or FF piglets. NK cells in SR piglets exhibited greater (P < 0.0001) cytotoxic activity than those in LF or FF piglets, which was supported by greater perforin mRNA expression. CONCLUSION: Dietary bLf increased blood NK cell populations and NK Lf receptor expression but not NK cell cytotoxicity.
Subject(s)
Infant Formula/pharmacology , Killer Cells, Natural/immunology , Lactation/immunology , Lactoferrin/pharmacology , Swine/immunology , Animals , Cattle , Dietary Supplements , Female , Flow Cytometry , Humans , Infant Formula/administration & dosage , Interleukin-2/immunology , K562 Cells , Killer Cells, Natural/drug effects , Lactoferrin/administration & dosage , Linear Models , Perforin/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND: The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. AIMS: We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. STUDY DESIGN AND SUBJECTS: 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. RESULTS: We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. CONCLUSIONS: These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway.
Subject(s)
Adipocytes/drug effects , Adipogenesis/drug effects , Lipids/pharmacology , Milk, Human/chemistry , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/metabolism , Animals , CCAAT-Enhancer-Binding Protein-beta/genetics , CCAAT-Enhancer-Binding Protein-beta/metabolism , Dexamethasone/pharmacology , Female , Humans , Infant , Infant Formula/pharmacology , Insulin/pharmacology , Mice , Tissue Inhibitor of Metalloproteinase-3/genetics , Tissue Inhibitor of Metalloproteinase-3/metabolismABSTRACT
Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS(-/-) mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate--a precursor for enteral generation of nitrite and nitric oxide--and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate-nitrite-NO signaling.
Subject(s)
Enterocolitis, Necrotizing/etiology , Intestinal Mucosa/blood supply , Microcirculation/physiology , Signal Transduction/physiology , Toll-Like Receptor 4/metabolism , Analysis of Variance , Animals , Animals, Newborn , Enterocolitis, Necrotizing/drug therapy , Enterocolitis, Necrotizing/metabolism , Infant Formula/chemistry , Infant Formula/pharmacology , Mice , Mice, Knockout , Microcirculation/drug effects , Microscopy, Confocal , Milk, Human/chemistry , Nitrates/analysis , Nitrates/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Nitrites/metabolism , Piperazines/pharmacology , Piperazines/therapeutic use , Purines/pharmacology , Purines/therapeutic use , Signal Transduction/drug effects , Sildenafil Citrate , Sulfones/pharmacology , Sulfones/therapeutic use , Toll-Like Receptor 4/deficiencyABSTRACT
BACKGROUND: Gastro-esophageal reflux (GER) is diagnosed frequently in preterm infants. Pharmacological treatment of GER has some potential side effects. Conservative treatment of GER should be the first-line approach and should include body positioning and diet modifications. Formula-fed preterm infants experience frequently symptoms of feeding intolerance. Hydrolyzed protein formula (HPF) is often used in these infants due to their effects on gastrointestinal motility. AIMS: To investigate the role of an extensively HPF (eHPF) on GER indexes in formula-fed preterm infants with symptoms of both GER and feeding intolerance. STUDY DESIGN: Randomized crossover trial. SUBJECTS: Preterm infants (gestational age ≤33 weeks) with symptoms of feeding intolerance (large gastric residuals, abdominal distension and constipation) and GER (frequent regurgitations and/or postprandial desaturations). OUTCOME MEASURES: GER indexes detected by 24-h combined multichannel intraluminal impedance and pH monitoring. GER indexes detected after 4 feeds of an eHPF were compared to those detected after 4 feeds of a standard preterm formula (SPF) by Wilcoxon signed ranks test. A p<0.05 was considered statistically significant. RESULTS: eHPF significantly reduced the number of GERs detected by pH monitoring (p=0.036) and also the reflux index (p=0.044) compared to SPF. No differences in impedance bolus exposure indexes nor in GER height were detected. CONCLUSIONS: The use of an eHPF should be evaluated for reducing esophageal acid exposure in preterm infants with feeding intolerance and symptoms of GER. Future research should focus on the evaluation of an eHPF adequate for preterm infants in improving clinical symptoms of GER.
Subject(s)
Gastroesophageal Reflux/diet therapy , Infant Formula/chemistry , Infant, Premature, Diseases/diet therapy , Protein Hydrolysates/administration & dosage , Cross-Over Studies , Female , Gastroesophageal Reflux/diagnosis , Humans , Infant Formula/pharmacology , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/diagnosis , MaleABSTRACT
BACKGROUND: Human milk is the gold standard of infant nutrition and is a source of important substances, including carotenoids. Infant formulas are designed to mimic the composition and/or performance of human milk, although currently carotenoids are not routinely added to US infant formulas. The aim of this study was to assess plasma concentrations of ß-carotene, lutein and lycopene 56 days after feeding infants milk-based infant formula without (CTRL) or with different concentrations of added carotenoids (L1 and L2). RESULTS: Plasma carotenoid concentrations increased in infants fed carotenoid-supplemented formulas as compared with the control formula with no added carotenoids. At study day 56, infants fed the supplemented formulas (L1 and L2) had mean plasma lutein, ß-carotene and lycopene concentrations that were within the range of a concurrent group of human milk-fed infants (HM). Anthropometric measurements were comparable among all study groups. CONCLUSION: Plasma carotenoid concentrations of infants fed the supplemented formulas were within the range of the HM group and are consistent with reported plasma carotenoid ranges in human milk-fed infants. The experimental formulas were well tolerated and anthropometric measurements were comparable among all study groups.
Subject(s)
Carotenoids/blood , Infant Formula/pharmacology , Milk/chemistry , Animals , Carotenoids/chemistry , Carotenoids/metabolism , Double-Blind Method , Female , Humans , Infant , Infant Formula/chemistry , Male , United StatesABSTRACT
Since type 1 diabetes is an immunologically mediated disease, immune intervention should alter the natural history of the disease. This article reviews prevention studies undertaken either prior to any evidence of autoimmunity (primary prevention) or after the development of islet autoantibodies (secondary prevention). Most immune intervention studies have been conducted in recent-onset type 1 diabetes (tertiary prevention), and these are not reviewed herein. The goal of primary and secondary intervention is to arrest the immune process and thus prevent or delay clinical disease. Primary prevention studies have been conducted in infants with high genetic risk. Interventions tested include several dietary manipulations, including infant formulas free of either cow's milk or of bovine insulin, infant formula supplemented with the omega-3-fatty acid docosahexaenoic acid, delayed introduction of gluten-containing foods, and vitamin D supplementation. Secondary prevention studies have been conducted in both children and adults with diabetes autoantibodies. Interventions tested include nicotinamide, insulin injections, oral insulin, nasal insulin, glutamic acid decarboxylase, and cyclosporine. Underway are secondary prevention studies with teplizumab and with abatacept.
Subject(s)
Diabetes Mellitus, Type 1/prevention & control , Diet/methods , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Primary Prevention , Secondary Prevention , Vitamin D/therapeutic use , Abatacept , Adolescent , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Autoantibodies/blood , Child , Child, Preschool , Cyclosporine/therapeutic use , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/therapy , Fatty Acids, Omega-3/administration & dosage , Female , Glutamate Decarboxylase/therapeutic use , Glutens/administration & dosage , Humans , Immunoconjugates/therapeutic use , Infant , Infant Formula/pharmacology , Infant, Newborn , Male , Niacinamide/therapeutic useABSTRACT
OBJECTIVE: To identify the effects of infant formula on the reproductive development of Spraque-Dawley rats. METHODS: A two-generation reproductive test was carried out. Forty 4 week-old SD rats were divided into two groups randomly by body weight and maintained on diet containing a kind of infant formula or an adjusted basal feeds. The body weight, dietary intake, hormone level, function of reproductive organs, and the development status of the P generation rats and F1 generation rats were measured. RESULTS: No significant growth-promoting effect was observed in the infant formula group; and no impairment on reproductive organ development or development status in the P generation and F1 generation rats was caused by the infant formula. The body weight at the 14th day of gestation and at the 0th and 4th day of lactation in infant formula group was significantly lower than that in control group (P < 0.05). The level of prolactin was significantly lower in the infant formula group. The AGD of F2a female rats was significantly shorter in the infant formula group. CONCLUSION: There was few effect of the infant formula on the reproductive development of SD rats, further study is required to determine the effects of infant formula on the body weight change during gestation period and lactation period, AGD and prolactin level.
Subject(s)
Body Weight/drug effects , Gonads/growth & development , Infant Formula/pharmacology , Animals , Female , Humans , Lactation , Rats , Rats, Sprague-Dawley , ReproductionABSTRACT
BACKGROUND: Human milk is the optimal nutrition for infants. When breastfeeding is not possible, supplementation of infant formula with long chain polyunsaturated fatty acids appears to promote neurodevelopmental outcome and visual function. Plant oils, that are the only source of fat in most of infant formulas, do not contain specific fatty acids that are present in human and cow milk and do not encounter milk fat triglyceride structure. Experimental data suggest that a mix of dairy lipids and plant oils can potentiate endogenous synthesis of n-3 long chain polyunsaturated fatty acids. This trial aims to determine the effect of an infant formula supplemented with a mixture of dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in full-term infants (primary outcome). Erythrocyte membrane long chain polyunsaturated fatty acids and fatty acids content, the plasma lipid profile and the insulin-growth factor 1 level, the gastrointestinal tolerance, the changes throughout the study in blood fatty acids content, in growth and body composition are evaluated as secondary outcomes. METHODS/DESIGN: In a double-blind controlled randomized trial, 75 healthy full-term infants are randomly allocated to receive for four months a formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils or a formula containing plant oils supplemented with arachidonic acid and docosahexaenoic acid. Twenty-five breast-fed infants constitute the reference group. Erythrocyte membrane omega-3 fatty acid profile, long chain polyunsaturated fatty acids and the other fatty acids content, the plasma lipid profile and the insulin-growth factor 1 level are measured after four months of intervention. Gastrointestinal tolerance, the changes in blood fatty acids content, in growth and body composition, assessed by means of an air displacement plethysmography system, are also evaluated throughout the study. DISCUSSION: The achievement of an appropriate long chain polyunsaturated fatty acids status represents an important goal in neonatal nutrition. Gaining further insight in the effects of the supplementation of a formula with dairy lipids and plant oils in healthy full-term infants could help to produce a formula whose fat content, composition and structure is more similar to human milk. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01611649.
Subject(s)
Dietary Supplements , Erythrocyte Membrane , Fatty Acids, Omega-3 , Infant Formula , Lipids , Plant Oils , Animals , Double-Blind Method , Erythrocyte Membrane/metabolism , Fatty Acids, Omega-3/metabolism , Humans , Infant Formula/pharmacology , Infant, Newborn , Lipids/pharmacology , Milk , Plant Oils/pharmacology , Term BirthABSTRACT
AIM: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy. METHOD: A double-blind, randomized control study was performed in two groups of healthy infants born at term: one group, constituting the control group, received standard formula (n=169) and another group received standard formula supplemented with LCPUFAs (n=146). A breastfed group (n=159) served as an additional reference. At 9 years of age, 72% of the children (control group: n=123; 71 males, 52 females; LCPUFA group: n=91; 42 males, 49 females; breastfed group: n=127, 64 males, 63 females) underwent extensive cognitive and behavioural testing. RESULTS: An interaction between infant nutrition and smoking during pregnancy was found. Among children exposed to smoking during pregnancy, LCPUFA supplementation was associated with higher mean verbal IQ scores (p=0.007) and learning and memory (p=0.006). Among children not exposed to smoking during pregnancy, LCPUFA supplementation was associated with lower mean verbal memory scores (p=0.003). Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group (p=0.001). Breastfeeding was associated with better performance on IQ (p=0.005). INTERPRETATION: No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found. The study confirmed that breastfeeding is associated with better cognition.