Growth and Gastrointestinal Tolerance in Healthy Term Infants Fed Milk-Based Infant Formula Supplemented with Five Human Milk Oligosaccharides (HMOs): A Randomized Multicenter Trial.

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2'-FL, 3-FL, LNT, 3'-SL and 6'-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.

Review of the Clinical Experiences of Feeding Infants Formula Containing the Human Milk Oligosaccharide 2'-Fucosyllactose.

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk after lactose and lipids. Preclinical research has demonstrated that HMOs and specifically 2'-fucosyllactose (2'-FL) are more than a prebiotic and have multiple functions, including immune, gut, and cognition benefits. Previously, human milk has been the only source for significant levels of HMOs. The most abundant HMO in most mothers' breast milk is 2'-FL. Recently, 2'-FL has been synthesized and shown to be structurally identical to the 2'-FL found in human milk. 2'-FL HMO is now available in some commercial infant formulas. The purpose of this narrative review was to summarize the clinical experiences of feeding infant formula supplemented with the HMO, 2'-FL. Most of these studies investigated standard intact milk protein-based infant formulas containing 2'-FL, and one evaluated a partially hydrolyzed whey-based formula. Collectively, these clinical experiences demonstrated that 2'-FL being added to infant formula was safe, well-tolerated, and absorbed and excreted with similar efficiency to 2'-FL in human milk. Further, infants that were fed formula with 2'-FL had immune benefits, fewer parent-reported respiratory infections, and improved symptoms of formula intolerance. Ultimately, infant formula with 2'-FL supports immune and gut health and is closer compositionally and functionally to human milk.

Effects of food unit size and energy density on intake in humans.

The effects of food unit size (FU) and energy density (ED) on food consumption were explored in 20 adults using a within subjects 2 x 2 design study. The four food treatment combinations were provided in the laboratory in random order on four non-consecutive days. The foods differed in FU (small food unit (SFU) or customary food unit (CFU)) and energy density, by manipulating fat content (low (LED) or high (HED)). Appetitive responses and total grams and kilocalories consumed were monitored. Hunger, fullness, desire to eat and prospective consumption ratings were not significantly different between treatments. Gram weight of food consumed was constant across all treatments. Energy intake of HED foods was greater than LED foods independent of food unit size for breakfast (F(1,17) = 11.77, p < 0.001), lunch (F(1,17) = 4.70, p < 0.05) and the 24 h period (F(1,17) = 8.99, p < 0.001) but only tended to be increased at dinner. In summary, appetitive sensations were not markedly altered by food unit size or energy density. The daily gram weight of food consumed and appetitive ratings were relatively consistent across treatments resulting in higher energy intake with HED foods.

Conjugated linoleic acids alter the fatty acid composition and physical properties of egg yolk and albumen.

Effects of dietary conjugated linoleic acids (CLAs) and docosahexaenoic acid (DHA) on the fatty acid composition of different egg compartments after storage were studied. Four dietary treatments [supplemented with safflower oil (SAFF, control group), DHA, CLAs plus DHA (CAD), and CLAs alone] were administered to Single Comb White Leghorn (SCWL) laying hens. Eggs from the different treatment groups were collected and stored for 10 weeks at 4 degrees C before analysis. Fatty acids from the yolk (yolk granules and plasma), egg albumen, and vitelline membrane were analyzed by gas chromatography. The yolk of eggs from hens given CLAs had significantly higher amounts of saturated fatty acids, typically 16:0 and 18:0, but lower amounts of polyunsaturated fatty acids (PUFAs) compared to eggs from the control group (SAFF). CLA content was highest in the yolk and present in both neutral and polar lipids, with the greatest concentrations in neutral lipids. DHA was incorporated mainly into yolk polar lipids. Lipids in yolk plasma and granules contained similar amounts of CLAs. The fatty acid compositions of vitelline membrane and egg albumen mirrored that of the egg yolk. CLA supplementation resulted in hard and rubbery yolks when compared to hard-cooked eggs from the control group. This study showed that feeding CLAs to hens led to accumulation of the isomers in polar and neutral lipids of the egg yolk and that these isomers migrated into egg albumen. Because the sensory properties of hard-cooked eggs were negatively affected by the enrichment of a mixture of CLA isomers in this study, further research should be conducted to evaluate how the different isomers alter the properties of egg yolk and albumen so that the quality of designed eggs containing CLAs and DHA can be improved.

Genetic and functional analysis of full-length human immunodeficiency virus type 1 env genes derived from brain and blood of patients with AIDS.

The genetic evolution of human immunodeficiency virus type 1 (HIV-1) in the brain is distinct from that in lymphoid tissues, indicating tissue-specific compartmentalization of the virus. Few primary HIV-1 envelope glycoproteins (Envs) from uncultured brain tissues have been biologically well characterized. In this study, we analyzed 37 full-length env genes from uncultured brain biopsy and blood samples from four patients with AIDS. Phylogenetic analysis of intrapatient sequence sets showed distinct clustering of brain relative to blood env sequences. However, no brain-specific signature sequence was identified. Furthermore, there was no significant difference in the number or positions of N-linked glycosylation sites between brain and blood env sequences. The patterns of coreceptor usage were heterogeneous, with no clear distinction between brain and blood env clones. Nine Envs used CCR5 as a coreceptor, one used CXCR4, and two used both CCR5 and CXCR4 in cell-to-cell fusion assays. Eight Envs could also use CCR3, CCR8, GPR15, STRL33, Apj, and/or GPR1, but these coreceptors did not play a major role in virus entry into microglia. Recognition of epitopes by the 2F5, T30, AG10H9, F105, 17b, and C11 monoclonal antibodies varied among env clones, reflecting genetic and conformational heterogeneity. Envs from two patients contained 28 to 32 N-glycosylation sites in gp120, compared to around 25 in lab strains and well-characterized primary isolates. These results suggest that HIV-1 Envs in brain cannot be distinguished from those in blood on the basis of coreceptor usage or the number or positions of N-glycosylation sites, indicating that other properties underlie neurotropism. The study also demonstrates characteristics of primary HIV-1 Envs from uncultured tissues and implies that Env variants that are glycosylated more extensively than lab strains and well-characterized primary isolates should be considered during development of vaccines and neutralizing antibodies.