Defining the lipid profiles of human milk, infant formula, and animal milk: implications for infant feeding.

Background: Breastfed infants have lower disease risk compared to formula-fed infants, however, the mechanisms behind this protection are unknown. Human milk has a complex lipidome which may have many critical roles in health and disease risk. However, human milk lipidomics is challenging, and research is still required to fully understand the lipidome and to interpret and translate findings. This study aimed to address key human milk lipidome knowledge gaps and discuss possible implications for early life health. Methods: Human milk samples from two birth cohorts, the Barwon Infant Study (n = 312) and University of Western Australia birth cohort (n = 342), were analysed using four liquid chromatography-mass spectrometry (LC-MS) methods (lipidome, triacylglycerol, total fatty acid, alkylglycerol). Bovine, goat, and soy-based infant formula, and bovine and goat milk were analysed for comparison. Composition was explored as concentrations, relative abundance, and infant lipid intake. Statistical analyses included principal component analysis, mixed effects modelling, and correlation, with false discovery rate correction, to explore human milk lipidome longitudinal trends and inter and intra-individual variation, differences between sample types, lipid intakes, and correlations between infant plasma and human milk lipids. Results: Lipidomics analysis identified 979 lipids. The human milk lipidome was distinct from that of infant formula and animal milk. Ether lipids were of particular interest, as they were significantly higher, in concentration and relative abundance, in human milk than in formula and animal milk, if present in the latter samples at all. Many ether lipids were highest in colostrum, and some changed significantly through lactation. Significant correlations were identified between human milk and infant circulating lipids (40% of which were ether lipids), and specific ether lipid intake by exclusively breastfed infants was 200-fold higher than that of an exclusively formula-fed infant. Conclusion: There are marked differences between the lipidomes of human milk, infant formula, and animal milk, with notable distinctions between ether lipids that are reflected in the infant plasma lipidome. These findings have potential implications for early life health, and may reveal why breast and formula-fed infants are not afforded the same protections. Comprehensive lipidomics studies with outcomes are required to understand the impacts on infant health and tailor translation.

Exposure to PCB126 during the nursing period reversibly impacts early-life glucose tolerance.

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal days (PND) 3, 10, and 17 (n = 9 per group). Offspring body weight, lean and fat mass, and glucose tolerance were recorded every three weeks. PCB126 treatment did not alter dam nor offspring body weight (p > 0.05). PCB126-exposed male and female offspring displayed normal body composition (p > 0.05) relative to vehicle-exposed offspring. However, both male and female offspring that were exposed to PCB126 during the nursing period had significantly impaired glucose tolerance at 3 and 9 weeks of age (p < 0.05). At 6 and 12 weeks of age, no impairments in glucose tolerance existed in offspring (p > 0.05). Our current study demonstrates that exposure to PCB126 through the mother's milk does not affect short- or long-term body composition but impairs glucose tolerance in the short-term.

Exposure to environmental contaminants and folic acid supplementation intergenerationally impact fetal skeleton development through the paternal lineage in a rat model.

Persistent organic pollutants (POPs) are ubiquitous in the environment, which is of concern since they are broadly toxic for wildlife and human health. It is generally accepted that maternal prenatal folic acid supplementation (FA) may beneficially impact offspring development, but it has been recently shown that the father's exposures also influence the health of his offspring. Bone is an endocrine organ essential for whole-body homeostasis and is susceptible to toxicants. Herein, we tested the hypotheses that prenatal paternal exposure to POPs induces developmental bone disorders in fetuses across multiple generations and that FA supplementation attenuates these disorders. We used a four-generation rat model, in which F0 founder females were divided into four treatment groups. F0 females were gavaged with corn oil or an environmentally-relevant POPs mixture and fed either a control diet (2 mg FA/kg), or FA supplemented diet (6 mg FA/kg) before mating and until parturition (four treatments in total). After the birth of the F1 litters, all F0 females and subsequent generations received the FA control diet. Staining with alcian blue and alizarin red S of male and female fetal skeletons was performed at Gestational Day 19.5. Paternal direct and ancestral exposure to POPs delayed bone ossification and decreased the length of long limb bones in fetuses. Maternal FA supplementation did not counteract the POPs-associated delayed fetal ossification and reduced long bone length. In conclusion, prenatal paternal POPs exposure causes developmental bone abnormalities over multiple generations, which were not corrected by maternal FA supplementation.

Prenatal Nicotine Exposure Induces Low Birthweight and Hyperinsulinemia in Male Rats.

Smoking during pregnancy is one of the causes of low birthweight. Ingestion of nicotine during pregnancy has various metabolic impacts on the fetus and offspring. According to the developmental origins of health and disease theory, low birthweight is a risk factor for developing various non-communicable diseases, including diabetes. We hypothesized that when nicotine-induced low-birthweight rats, when exposed to a high-fat diet (HFD) after growth, are predisposed to glucose intolerance as a result of a mismatch between the eutrophic environment and small body size. Therefore, we investigated whether hyperinsulinemia was caused by exposure of nicotine-induced low-birthweight rats to HFD, including whether this phenomenon exhibited possible sex differences. The average birthweight and body weight at weaning day of offspring from nicotine-administered dams was lower than those of controls. The offspring from nicotine-administered dams did not show rapid fat accumulation after exposure to HFD, and weight and body fat ratio of these animals did not differ from those of the controls. Blood glucose levels did not differ between the groups, but insulin levels increased only in male HFD-exposed offspring from nicotine-administered dams. Similarly, only in HFD-exposed male from nicotine-administered dams showed decreases in the insulin receptor expression in the liver. We conclude that male rats subjected to prenatal nicotine exposure develop hyperinsulinemia when exposed to HFD after growth. Our results suggest that decreased expression of insulin receptors in the liver may be involved in the mechanism underlying hyperinsulinemia in low-birthweight offspring, a phenomenon that appeared to exhibit a sex-specific bias.

Maternal High-Fat Diet Alters the Characteristics of Astrocytes and Worsens the Outcome of Stroke in Rat Offspring, Which Improves After FGF21 Administration.

Background: Maternal high-fat diet (MHFD) has been shown to increase susceptibility to neurological disease in later offspring, but the underlying mechanism is not clear. Fibroblast growth factor 21 (FGF21) has been reported to have a neuroprotective effect in stroke, but its mechanism of action remains unknown. In this study, we investigated the mechanism of the effect of MHFD on stroke in offspring in adulthood and the mechanism by which FGF21 acts on stroke and restores neurological function. Methods: We performed transcriptome sequencing analysis on D21 neonatal rats. Bodyweight and blood indicators were recorded in the adult rats after MHFD. FGF21 was administered 7 h after photochemical modeling twice a day for three consecutive days. Results: We found numerous mRNA changes between the MHFD group and a normal maternal normal diet (MND) group at D21, including genes related to astrocyte and PI3K/Akt pathways. The body weight, blood glucose, and triglycerides of the MHFD offspring were higher, ischemic lesions were larger, the number of activated astrocytes was lower, and the neurological function score was worse than that of the MND group. After FGF21 administration, WB and qPCR analyses showed that astrocytes and the PI3K/Akt pathway were upregulated, while NF-κB and inflammatory cytokines expression were inhibited in stroke and peri-stroke regions. Conclusion: Taken together, we conclude that MHFD alters the characteristics of astrocytes and other transcriptome changes in their offspring, leading to a worse prognosis of stroke, while FGF21 plays a neuroprotective role by inhibiting NF-κB and inflammatory factors and activating the PI3K/Akt pathway and activating more astrocytes in the MND group than the MHFD group.

Maternal Microbiota Transfer Programs Offspring Eating Behavior.

Understanding the link between mother's obesity and regulation of the child's appetite is a prerequisite for the design of successful preventive strategies. Beyond the possible contributions of genetic heritage, family culture, and hormonal and metabolic environment during pregnancy, we investigate in the present paper the causal role of the transmission of the maternal microbiotas in obesity as microbiotas differ between lean and obese mothers, maternal microbiotas are the main determinants of a baby's gut colonization, and the intestinal microbiota resulting from the early colonization could impact the feeding behavior of the offspring with short- and long-term consequences on body weight. We thus investigated the potential role of vertical transfers of maternal microbiotas in programming the eating behavior of the offspring. Selectively bred obese-prone (OP)/obese-resistant (OR) Sprague-Dawley dams were used since differences in the cecal microbiota have been evidenced from males of that strain. Microbiota collected from vagina (at the end of gestation), feces, and milk (at postnatal days 1, 5, 10, and 15) of OP/OR dams were orally inoculated to conventional Fischer F344 recipient pups from birth to 15 days of age to create three groups of pups: F-OP, F-OR, and F-Sham group (that received the vehicle). We first checked microbiotal differences between inoculas. We then assessed the impact of transfer (from birth to adulthood) onto the intestinal microbiota of recipients rats, their growth, and their eating behavior by measuring their caloric intake, their anticipatory food reward responses, their preference for sweet and fat tastes in solutions, and the sensations that extend after food ingestion. Finally, we searched for correlation between microbiota composition and food intake parameters. We found that maternal transfer of microbiota differing in composition led to alterations in pups' gut microbiota composition that did not last until adulthood but were associated with specific eating behavior characteristics that were predisposing F-OP rats to higher risk of over consuming at subsequent periods of their life. These findings support the view that neonatal gut microbiotal transfer can program eating behavior, even without a significant long-lasting impact on adulthood microbiota composition.

Precision Nutrition and Childhood Obesity: A Scoping Review.

Environmental exposures such as nutrition during life stages with high developmental plasticity-in particular, the in utero period, infancy, childhood, and puberty-may have long-lasting influences on risk of chronic diseases, including obesity-related conditions that manifest as early as childhood. Yet, specific mechanisms underlying these relationships remain unclear. Here, we consider the study of 'omics mechanisms, including nutrigenomics, epigenetics/epigenomics, and metabolomics, within a life course epidemiological framework to accomplish three objectives. First, we carried out a scoping review of population-based literature with a focus on studies that include 'omics analyses during three sensitive periods during early life: in utero, infancy, and childhood. We elected to conduct a scoping review because the application of multi-'omics and/or precision nutrition in childhood obesity prevention and treatment is relatively recent, and identifying knowledge gaps can expedite future research. Second, concomitant with the literature review, we discuss the relevance and plausibility of biological mechanisms that may underlie early origins of childhood obesity identified by studies to date. Finally, we identify current research limitations and future opportunities for application of multi-'omics in precision nutrition/health practice.