Daily protein and energy intakes of infants fed a commercial infant formula with a reduced protein concentration of 2.2 g/100 kcal: an impact of feeding interval on energy intake.

We evaluated the protein and energy intakes of infants fed commercial infant Formula A (protein, 2.2 g/100 kcal; energy, 68 kcal/100 mL) and examined whether changes in feeding intervals are involved in constant energy intake. Daily nutritional intake of 378 Formula A-fed infants was assessed using reference values and compared to that of infants fed Formulas B (protein: 2.3 g/100 kcal, energy: 68 kcal/100 mL) and C (protein: 2.4 g/100kcal, energy: 70 kcal/100 mL). From 15 to 149 days of age, the mean formula volume and protein intake were 758-887 mL/day and 11.4-13.3 g/day, respectively, higher than the protein intake of breast-fed infants. Daily energy intake (86-129 kcal/kg/day) was comparable to the estimated energy requirements. Feeding intervals were shorter in infants fed Formulas A and B than in those fed Formula C, whereas energy intake was similar. The protein intake of infants decreased as the protein concentration per energy in infant formula was reduced, and accordingly the protein intake of Formula A-fed infants was significantly lower than that of Formula C-fed infants. In conclusion, the new composition of Formula A is suitable in protein and energy intake of infants, and daily energy intake remains constant by shortening in feeding intervals when the energy concentration in infant formula is reduced.Clinical Trial Registration: UMIN000023110.

Growth of term infants fed a commercial infant formula with a protein content of 2.2 g/100 kcal: an observational follow-up study.

To evaluate the suitability of the new nutritional composition of renewed commercial Formula A (protein reduced to 2.2 g/100 kcal, arachidonic acid increased to 13.2 mg/100 kcal, and docosahexaenoic acid maintained at 20 mg/100 kcal), we examined whether the growth of Formula A-fed infants was equivalent to that of breastfed infants. In this observational study, 1,053 infants were followed-up to 12 months. Growth, stool consistency, and the health condition of 99 infants fed with Formula A and 295 breastfed infants were compared. Body weight, body mass index, and head circumference of Formula A-fed infants were similar to those of breastfed infants. Additionally, there were no differences in the stool consistency and the health condition (infection and allergy prevalence) between the two groups. Formula A-fed infants grew as well as breastfed infants, suggesting the appropriate nutritional composition of Formula A. The findings may contribute to further improvements in infant formulas.

Postnatal weight gain induced by overfeeding pups and maternal high-fat diet during the lactation period modulates glucose metabolism and the production of pancreatic and gastrointestinal peptides.

The impact of rapid weight gain on glucose metabolism during the early postnatal period remains unclear. We investigated the influence of rapid weight gain under different nutritional conditions on glucose metabolism, focusing on the production of pancreatic and gastric peptides. On postnatal day (PND) 2, C57BL/6N pups were divided into three groups: control (C) pups whose dams were fed a control diet (10%kcal fat) and nursed 10 pups each; maternal high-fat diet (HFD) pups whose dams were fed an HFD (45%kcal fat) and nursed 10 pups each; and overfeeding (OF) pups whose dams were fed the control diet and nursed 4 pups each. Data were collected on PND 7, 14 and 21. The body weight gains of the HFD and OF pups were 1.2 times higher than that of the C pups. On PND 14, the HFD pups had higher blood glucose levels, but there were no significant differences in serum insulin levels between the HFD and C pups. The OF pups had higher blood glucose and serum insulin levels than that of the C pups. Insulin resistance was found in the HFD and OF pups. On PND 14, the content of incretins in the jejunum was increased in the OF pups, and acyl ghrelin in the stomach was upregulated in the HFD and OF pups. These results suggest that neonatal weight gain induced by overfeeding pups and maternal high-fat diet during the early postnatal period modulates the insulin sensitivity and the production of pancreatic and gastrointestinal peptides.

Large molecule protein feeding during the suckling period is required for the development of pancreatic digestive functions in rats.

We examined if large molecule protein feeding during the suckling period is prerequisite for the proper development of pancreatic digestive functions. Most amino acids in breast milk exist as the constituent of large proteins and not as oligopeptides or free amino acids. Accumulating evidence indicates the nutritional importance of large protein feeding for suckling infants; however, evidence on the physiological significance remains small. We thus artificially reared rat pups on a standard rat formula with milk protein or a formula with milk protein hydrolysate from 7 to 21 days of age, and thereafter, fed a standard solid diet until 42 days of age. Pancreas weight and the stock of pancreatic digestive enzymes in the hydrolysate-fed rats were significantly lower than those in the protein-fed rats during and also after the suckling period. Plasma insulin, a stimulator of amylase synthesis, was also significantly low in the hydrolysate-fed rats compared with the protein-fed rats. At 28 days of age, we evaluated the pancreatic secretory ability in response to dietary protein and cholecystokinin (CCK) by means of pancreatic duct cannulation. Pancreatic secretion stimulated by dietary protein in the hydrolysate-fed rats was significantly weaker than that in the protein-fed rats. No significant difference was observed in the increasing rate of pancreatic enzyme secretion in response to CCK between the two groups. These results suggest that the presence of large proteins in breast milk is significant for the development of pancreatic digestive functions and the outcomes could remain even later on in life.

Bifidobacterium bifidum reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of neonates, and clinical studies suggest the beneficial effect of probiotics in NEC prevention. Recently, we have shown that administration of Bifidobacterium bifidum protects against NEC in a rat model. Intestinal apoptosis can be suppressed by activation of cyclooxygenase-2 (COX-2) and increased production of prostaglandin E(2) (PGE(2)). The present study investigates the effect of B. bifidum on intestinal apoptosis in the rat NEC model and in an intestinal epithelial cell line (IEC-6), as a mechanism of protection against mucosal injury. Premature rats were divided into the following three groups: dam fed, hand fed with formula (NEC), or hand fed with formula supplemented with B. bifidum (NEC + B. bifidum). Intestinal Toll-like receptor-2 (TLR-2), COX-2, PGE(2), and apoptotic regulators were measured. The effect of B. bifidum was verified in IEC-6 cells using a model of cytokine-induced apoptosis. Administration of B. bifidum increased expression of TLR-2, COX-2, and PGE(2) and significantly reduced apoptosis in the intestinal epithelium of both in vivo and in vitro models. The Bax-to-Bcl-w ratio was shifted toward cell survival, and the number of cleaved caspase-3 positive cells was markedly decreased in B. bifidum-treated rats. Experiments in IEC-6 cells showed anti-apoptotic effect of B. bifidum. Inhibition of COX-2 signaling blocked the protective effect of B. bifidum treatment in both in vivo and in vitro models. In conclusion, oral administration of B. bifidum activates TLR-2 in the intestinal epithelium. B. bifidum increases expression of COX-2, which leads to higher production of PGE(2) in the ileum and protects against intestinal apoptosis associated with NEC. This study indicates the ability of B. bifidum to downregulate apoptosis in the rat NEC model and in IEC-6 cells by a COX-2-dependent matter and suggests a molecular mechanism by which this probiotic reduces mucosal injury and preserves intestinal integrity.

Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis.

Neonatal necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants. Oral administration of probiotics has been suggested as a promising strategy for prevention of NEC. However, little is known about the mechanism(s) of probiotic-mediated protection against NEC. The aim of this study was to evaluate the effects of Bifidobacterium bifidum treatment on development of NEC, cytokine regulation, and intestinal integrity in a rat model of NEC. Premature rats were divided into three groups: dam fed (DF), hand fed with formula (NEC), or hand fed with formula supplemented with 5 x 10(6) CFU B. bifidum per day (B. bifidum). All groups were exposed to asphyxia and cold stress to develop NEC. Intestinal injury, mucin and trefoil factor 3 (Tff3) production, cytokine levels, and composition of tight junction (TJ) and adherens junction (AJ) proteins were evaluated in the terminal ileum. B. bifidum decreased the incidence of NEC from 57 to 17%. Increased levels of IL-6, mucin-3, and Tff3 in the ileum of NEC rats was normalized in B. bifidum treated rats. Reduced mucin-2 production in the NEC rats was not affected by B. bifidum. Administration of B. bifidum normalized the expression and localization of TJ and AJ proteins in the ileum compared with animals with NEC. In conclusion, administration of B. bifidum protects against NEC in the neonatal rat model. This protective effect is associated with reduction of inflammatory reaction in the ileum, regulation of main components of mucus layer, and improvement of intestinal integrity.