Optimal Protein Intake in Healthy Children and Adolescents: Evaluating Current Evidence.

High protein intake might elicit beneficial or detrimental effects, depending on life stages and populations. While high protein intake in elder individuals can promote beneficial health effects, elevated protein intakes in infancy are discouraged, since they have been associated with obesity risks later in life. However, in children and adolescents (4-18 years), there is a scarcity of data assessing the effects of high protein intake later in life, despite protein intake being usually two- to three-fold higher than the recommendations in developed countries. This narrative review aimed to revise the available evidence on the long-term effects of protein intake in children and adolescents aged 4-18 years. Additionally, it discusses emerging techniques to assess protein metabolism in children, which suggest a need to reevaluate current recommendations. While the optimal range is yet to be firmly established, available evidence suggests a link between high protein intake and increased Body Mass Index (BMI), which might be driven by an increase in Fat-Free Mass Index (FFMI), as opposed to Fat Mass Index (FMI).

Physiological Impact of Palm Olein or Palm Oil in Infant Formulas: A Review of Clinical Evidence.

Palm oil/olein (PO/POL) is used in infant formulas to imitate the fatty acid profile of human milk (HM) and achieve similar levels of palmitic acid (PA). However, the positions of fatty acids on the triacylglyceride differ between PO/POL and HM, which affect fat absorption and produce unintended physiological consequences. Recent papers have reviewed evidence for physiological benefits of PO/POL and beta-palmitate (sn-2-palmitate) in infant formulas. The aim of the present review is to supplement the assessment of available clinical evidence on the physiological effects of PO/POL formulas in healthy infants. We intend to focus on PO/POL and not on sn-2-palmitate, since the latter was recently extensively reviewed. Clinical evidence supports that PO/POL in infant formulas leads to a lower fat, DHA, palmitate and calcium absorption, and bone mineralization; soft stools; and growth (weight accretion) compared to formulas without PO/POL. Consequently, it seems prudent to be considerate and cautious when adding PO/POL to infant formulas. While HM is the gold standard for infant nutrition, the development of infant formula should be based on achieving positive physiological outcomes, rather than just replicating HM nutrient composition.

Systematic review indicates postnatal growth in term infants born small-for-gestational-age being associated with later neurocognitive and metabolic outcomes.

We systematically reviewed papers published in English between 1994 and October 2015 on how postnatal weight gain and growth affect neurodevelopment and metabolic outcomes in term-born small-for-gestational-age (SGA) infants. Two randomised trials reported that enriched infant formulas that promoted early growth also increased fat mass, lean mass and blood pressure (BP), but had no effect on early neurocognitive outcomes. Meanwhile, 31 observational studies reported consistent positive associations between postnatal weight gain and growth with neurocognitive outcomes, adiposity, insulin resistance and BP. CONCLUSION: Few intervention studies exist, despite consistent positive associations between early growth and neurocognition in term-born SGA infants.

Building a Beneficial Microbiome from Birth.

The microbiota has recently been recognized as a driver of health that affects the immune, nervous, and metabolic systems. This influence is partially exerted through the metabolites produced, which may be relevant for optimal infant development and health. The gut microbiota begins developing early in life, and this initial colonization is remarkably important because it may influence long-term microbiota composition and activity. Considering that the microbiome may play a key role in health and disease, maintaining a protective microbiota could be critical in preventing dysbiosis-related diseases such as allergies, autoimmunity disorders, and metabolic syndrome. Breast milk and milk glycans in particular are thought to play a major role in shaping the early-life microbiota and promoting its development, thus affecting health. This review describes some of the effects the microbiota has on the host and discusses the role microbial metabolites play in shaping newborn health and development. We describe the gut microbiota structure and function during early life and the factors that determine its composition and hypothesize about the effects of human milk oligosaccharides and other prebiotic fibers on the neonatal microbiota.

2'-fucosyllactose: an abundant, genetically determined soluble glycan present in human milk.

Lactose is the preeminent soluble glycan in milk and a significant source of energy for most newborn mammals. Elongation of lactose with additional monosaccharides gives rise to a varied repertoire of free soluble glycans such as 2'-fucosyllactose (2'-FL), which is the most abundant oligosaccharide in human milk. In infants, 2'-FL is resistant to digestion and reaches the colon where it is partially fermented, behaving as soluble prebiotic fiber. Evidence also suggests that portions of small soluble milk glycans, including 2'-FL, are absorbed, thus raising the possibility of systemic biological effects. 2'-FL bears an epitope of the Secretor histo-blood group system; approximately 70-80% of all milk samples contain 2'-FL, since its synthesis depends on a fucosyltransferase that is not uniformly expressed. The fact that some infants are not exposed to 2'-FL has helped researchers to retrospectively probe for biological activities of this glycan. This review summarizes the attributes of 2'-FL in terms of its occurrence in mammalian phylogeny, its postulated biological activities, and its variability in human milk.

Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor.

Metacaspases are caspase family cysteine peptidases found in plants, fungi, and protozoa but not mammals. Trypanosoma brucei is unusual in having five metacaspases (MCA1-MCA5), of which MCA1 and MCA4 have active site substitutions, making them possible non-enzymatic homologues. Here we demonstrate that recombinant MCA4 lacks detectable peptidase activity despite maintaining a functional peptidase structure. MCA4 is expressed primarily in the bloodstream form of the parasite and associates with the flagellar membrane via dual myristoylation/palmitoylation. Loss of function phenotyping revealed critical roles for MCA4; rapid depletion by RNAi caused lethal disruption to the parasite's cell cycle, yet the generation of MCA4 null mutant parasites (Δmca4) was possible. Δmca4 had normal growth in axenic culture but markedly reduced virulence in mice. Further analysis revealed that MCA4 is released from the parasite and is specifically processed by MCA3, the only metacaspase that is both palmitoylated and enzymatically active. Accordingly, we have identified that the multiple metacaspases in T. brucei form a membrane-associated proteolytic cascade to generate a pseudopeptidase virulence factor.

Characterization of an ABCG-like transporter from the protozoan parasite Leishmania with a role in drug resistance and transbilayer lipid movement.

Leishmaniasis treatment is hampered by the increased appearance of treatment failure. ATP-binding cassette (ABC) transporters are usually involved in drug resistance both in tumor cells and in microorganisms. Here we report the characterization of an ABCG-like transporter, LiABCG6, localized mainly at the plasma membrane in Leishmania protozoan parasites. When overexpressed, this half-transporter confers significant resistance to the leishmanicidal agents miltefosine and sitamaquine. This resistance phenotype is mediated by a reduction in intracellular drug accumulation. LiABCG6 also reduces the accumulation of short-chain fluorescent phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. As a whole, these results suggest that LiABCG6 could be implicated in phospholipid trafficking and drug resistance.

A novel ATP-binding cassette transporter from Leishmania is involved in transport of phosphatidylcholine analogues and resistance to alkyl-phospholipids.

ATP-binding cassette (ABC) transporters represent an important family of membrane proteins involved in drug resistance and other biological activities. The present work reports the characterization of the first ABC subfamily G (ABCG)-like transporter, LiABCG4, in the protozoan parasite Leishmania. LiABCG4 localized mainly to the parasite plasma membrane. Overexpression of this half-transporter reduced the accumulation of phosphatidylcholine analogues and conferred resistance to alkyl-phospholipids. Likewise, when expressed in Saccharomyces cerevisiae, the protein localized to the yeast plasma membrane and conferred resistance to alkyl-phospholipids. Post-Golgi secretory vesicles isolated from a LiABCG4-overexpressing yeast mutant contained the leishmanial ABC transporter and exhibited ATP-dependent, vanadate-sensitive transport of phosphatidylcholine analogues from the cytosolic to the lumenal leaflet of the vesicle membrane. Cross-linking showed dimerization of LiABCG4. These results suggest that LiABCG4 is involved in the active transport of phosphatidylcholine and resistance to alkyl-phospholipids in Leishmania.