Ricardo Rueda

Addition of gangliosides to an adapted milk formula modifies levels of fecal Escherichia coli in preterm newborn infants

Because some gangliosides bind bacteria, we tested the influence of supplementating an adapted milk formula with gangliosides, at a total concentration of 1.43 mg/100 kcal, on the fecal microflora of preterm infants. At all sampling times, feces from infants fed with ganglioside-supplemented formula had significantly lower relative content of Escherichia coli than feces from infants fed with control milk formula: the difference was especially significant at age 7 days postnatal < .001). At age 30 days postnatal, fecal bifidobacterial counts were higher in infants fed with ganglioside-supplemented formula (P < .05). We conclude that gangliosides at concentrations present in human milk significantly modify the fecal flora.

Decreased levels of circulating CD4 ÷ T lymphocytes during normal human pregnancy

Peripheral blood mononuclear cell (PBMC) populations during human pregnancy have been investigated by many authors, although the different results obtained, principally in relation to T cells, are very discrepant. In this study we aimed to exclude all the possible causes of these discrepancies: small sample size; diurnal rhythm of CD4+ T cells; smoking habits; haemodilution which occurs during pregnancy and inappropriate statistical analysis; in order to determine whether gestation has a definite effect on PBMC populations. We found that the percentage of CD4+ T lymphocytes decreases in the first and second trimesters, returns to the non-pregnant level in the third trimester and remains there in the postpartum period. The percentages of CD3+ T lymphocytes run parallel to those of CD4+ while CD8+ T lymphocytes do not vary. The proportion of CD16+ cells, which include mature NK cells, diminishes in the second trimester and this reduction is maintained in the third trimester and the puerperium. No variation was found in the other PBMC studied (CD20+ lymphocytes, CD14+ monocytes and D/DR+ cells). When parity was considered no difference was seen between primiparous and multiparous women in any of the cell populations tested.

Neonatal dietary gangliosides

Gangliosides are glycosphingolipids that are widely distributed in vertebrate tissues and body fluids and which are specially abundant in neural tissues. Milk from different species has a particular ganglioside content and profile. Human milk has a higher content of gangliosides than bovine milk. GD3 and GM3 are the predominant individual gangliosides in bovine milk. In human colostrum GD3 is also the main ganglioside whereas in human mature milk GM3 predominates over the other gangliosides. Human milk also contains GM1 and a number of highly polar gangliosides, which may play an important role in infant physiology. GM1 has been shown to inhibit Escherichia coli and Vibrio cholerae enterotoxins. We have found that a ganglioside-supplemented infant formula modifies the intestinal ecology of preterm newborns, increasing the Bifidobacteria content and lowering that of Escherichia coli. Although the exact mechanism by which dietary gangliosides reduce the fecal content of Escherichia coli is unknown, in vitro experiments suggest that they may act as false intestinal receptors for some strains of this bacteria. Since GD3 and other gangliosides have been involved in mechanisms of lymphocyte activation and differentiation, dietary gangliosides might have a function in intestinal immunity development.

Interaction of early diet and the development of the immune system

The present review focuses on the specific effects of nutrients on the development of the immune system in early life. There is a big gap regarding the specific mechanisms that regulate immunity at the intestinal level and their impact in the systemic immune function. For this reason, during the last few years there has been great interest in ascertaining the mechanisms that regulate the intestinal immune function, as well as to understand how specific nutrients interact with the gut-associated lymphoid tissue. We have reviewed this topic with special emphasis on how human milk, and its components, influence the early development of intestinal immunity in breast-fed infants compared with formula-fed infants. Interactions between nutrients and intestinal microbiota have also been reviewed. Some micronutrients such as nucleotides and gangliosides, which are present in human milk and also in most foods, are able to influence immune functionality at very low concentrations. The specific action of these micronutrients on some parameters of immunity, as well as their potential mechanisms of action, have been considered in detail. However, there are limited data on how other specific nutrients, namely protein and non-protein N-containing compounds, lipids, carbohydrates, and others, such as minerals, vitamins, fibre, non-nutritional dietary compounds (flavonoids, carotenoids, phyto-oestrogens, etc), influence immunity. In the present review we have provided data regarding the potential effects of these compounds on the immune response in early life. The increasing use of functional foods by the public to improve their general health and prevent the incidence of chronic diseases has become a major area of interest within the nutrition community. Of the many functional foods available, probiotics have been most studied in infancy and childhood, particularly with regard to the prevention of allergic diseases. Infant formulae and fermented milks containing large quantities of probiotics are produced and consumed by Europeans and in other industrialized countries. In the present review we cover the clinical effects of probiotics in preventing disease during early life, as well as the potential mechanisms of interaction between probiotics and the gastrointestinal tract.

Gestational age and origin of human milk influence total lipid and fatty acid contents.

The human milk composition may be influenced by several factors, such as gestational age or genetic characteristics and dietary habits of different populations. To analyze the total lipid and fatty acid contents of human milk, we have conducted two studies, one on mothers who had delivered preterm and term newborns and another on mothers from two different sociocultural backgrounds (Spain and Panama). The total lipid content (g/100 g wet weight) was significantly higher in term (2.76 ± 0.66; mean ± SD) than in preterm mature milk (1.06 ± 0.4). The relative amount of 18:1n-9 was significantly higher in preterm than in term milk for transitional and mature milk, whereas that for the colostrum followed the opposite trend. Concerning the comparison between milk from mothers born in different countries, the relative contents of each of the fatty acids 16:0, 16:1n-7, 18:2n-6, 18:3n-3, and 22:5n-3 were higher in Panamanian than in Spanish milk, whereas the mean percentages of saturated fatty acids <14:0, of 16:1n-9, and of 18:1n-9 were higher in Spanish than in Panamanian milk. Statistically significant differences were found during the three periods of lactation considered for almost all the fatty acids mentioned above, especially for 18:1n-9 and 18:3n-3. Although the potential biological significance of the changes in oleic acid content between preterm and term milk remains unclear, differences in fatty acid content between Spanish and Panamanian milk reflect the different composition of the diet among women from these countries.

Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease

Skeletal muscle is recognized as vital to physical movement, posture, and breathing. In a less known but critically important role, muscle influences energy and protein metabolism throughout the body. Muscle is a primary site for glucose uptake and storage, and it is also a reservoir of amino acids stored as protein. Amino acids are released when supplies are needed elsewhere in the body. These conditions occur with acute and chronic diseases, which decrease dietary intake while increasing metabolic needs. Such metabolic shifts lead to the muscle loss associated with sarcopenia and cachexia, resulting in a variety of adverse health and economic consequences. With loss of skeletal muscle, protein and energy availability is lowered throughout the body. Muscle loss is associated with delayed recovery from illness, slowed wound healing, reduced resting metabolic rate, physical disability, poorer quality of life, and higher health care costs. These adverse effects can be combatted with exercise and nutrition. Studies suggest dietary protein and leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance. Considerable evidence shows that use of high-protein oral nutritional supplements (ONS) can help maintain and rebuild muscle mass and strength. We review muscle structure, function, and role in energy and protein balance. We discuss how disease- and age-related malnutrition hamper muscle accretion, ultimately causing whole-body deterioration. Finally, we describe how specialized nutrition and exercise can restore muscle mass, strength, and function, and ultimately reverse the negative health and economic outcomes associated with muscle loss.

β-Hydroxy-β-Methylbutyrate (HMB) Normalizes Dexamethasone-Induced Autophagy-Lysosomal Pathway in Skeletal Muscle

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

Conversion of leucine to β-hydroxy-β-methylbutyrate by α-keto isocaproate dioxygenase is required for a potent stimulation of protein synthesis in L6 rat myotubes

L‐Leu and its metabolite β‐hydroxy‐β‐methylbutyrate (HMB) stimulate muscle protein synthesis enhancing the phosphorylation of proteins that regulate anabolic signalling pathways. Alterations in these pathways are observed in many catabolic diseases, and HMB and L‐Leu have proven their anabolic effects in in vivo and in vitro models. The aim of this study was to compare the anabolic effects of L‐Leu and HMB in myotubes grown in the absence of any catabolic stimuli.

Developmental Changes in UDP-N-Acetylglucosamine 2-Epimerase Activity of Rat and Guinea-Pig Liver

The activity of UDP-N-acetylglucosamine 2-epimerase was determined in the liver of rats and guinea-pigs of different ages. The activity of this enzyme in rats was low at birth, increased to a maximum value on day 15, and fell gradually until day 30. Thereafter, it increased up to the 60th day. The activity profile of the enzyme from guinea-pig liver was very similar. However, guinea-pig activity was 2-5 times lower than in rats. Both rats and guinea-pigs displayed similar liver sialic acid contents which increased from birth to 2 months of age. Rats also showed a N-glycolylneuraminic acid content that decreased from birth to 2 months. From these results we can inferred that postnatal UDP-N-acetylglucosamine 2-epimerase activity seems to be correlated with age and the developmental states of rats and guinea-pigs.

Maternal Diabetes and Cognitive Performance in the Offspring: A Systematic Review and Meta-Analysis.

Objective Diabetes during gestation is one of the most common pregnancy complications associated with adverse health effects for the mother and the child. Maternal diabetes has been proposed to negatively affect the cognitive abilities of the child, but experimental research assessing its impact is conflicting. The main aim of our study was to compare the cognitive function in children of diabetic and healthy pregnant women. Methods A systematic review and meta-analysis was conducted through a literature search using different electronic databases from the index date to January 31, 2015. We included studies that assessed the cognitive abilities in children (up to 14 years) of diabetic and non-diabetic mothers using standardized and validated neuropsychological tests. Results Of 7,698 references reviewed, 12 studies involving 6,140 infants met our inclusion criteria and contributed to meta-analysis. A random effect model was used to compute the standardized mean differences and 95% confidence interval (CI) were calculated. Infants (1–2 years) of diabetic mothers had significantly lower scores of mental and psychomotor development compared to control infants. The effect size for mental development was -0.41 (95% CI -0.59, -0.24; p<0.0001) and for psychomotor development was -0.31 (95% CI -0.55, -0.07; p = 0.0125) with non-significant heterogeneity. Diabetes during pregnancy could be associated with decreased intelligence quotient scores in school-age children, although studies showed significant heterogeneity. Conclusion The association between maternal diabetes and deleterious effects on mental/psychomotor development and overall intellectual function in the offspring must be taken with caution. Results are based on observational cohorts and a direct causal influence of intrauterine hyperglycemia remains uncertain. Therefore, more trials that include larger populations are warranted to elucidate whether gestational diabetes mellitus (GDM) has a negative impact on offspring central nervous system (CNS).