Levels of Breast Milk MicroRNAs and Other Non-Coding RNAs Are Impacted by Milk Maturity and Maternal Diet

There is emerging evidence that non-coding RNAs (ncRNAs) within maternal breast milk (MBM) impart unique metabolic and immunologic effects on developing infants. Most studies examining ncRNAs in MBM have focused on microRNAs. It remains unclear whether microRNA levels are related to other ncRNAs, or whether they are impacted by maternal characteristics. This longitudinal cohort study examined 503 MBM samples from 192 mothers to: 1) identify the most abundant ncRNAs in MBM; 2) examine the impact of milk maturity on ncRNAs; and 3) determine whether maternal characteristics affect ncRNAs. MBM was collected at 0, 1, and 4 months post-delivery. High throughput sequencing quantified ncRNAs within the lipid fraction. There were 3069 ncRNAs and 238 microRNAs with consistent MBM presence (≥10 reads in ≥10% samples). Levels of 17 ncRNAs and 11 microRNAs accounted for 80% of the total RNA content. Most abundant microRNAs displayed relationships ([R]>0.2, adj p< 0.05) with abundant ncRNAs. A large proportion of ncRNAs (1269/3069; 41%) and microRNAs (206/238; 86%) were affected by MBM maturity. The majority of microRNAs (111/206; 54%) increased from 0-4 months. Few ncRNAs and microRNAs were affected (adj p < 0.05) by maternal age, race, parity, body mass index, gestational diabetes, or collection time. However, nearly half of abundant microRNAs (4/11) were impacted by diet. To our knowledge this is the largest study of MBM ncRNAs, and the first to demonstrate a relationship between MBM microRNAs and maternal diet. Such knowledge could guide nutritional interventions aimed at optimizing metabolic and immunologic microRNA profiles within MBM.

Maternal diet-induced obesity during pregnancy alters lipid supply to mouse E18.5 fetuses and changes the cardiac tissue lipidome in a sex-dependent manner

Maternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in late gestation E18.5 fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female fetal heart lipidomes are more sensitive to maternal obesity than males; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.

Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring

Various environmental exposures during pregnancy, like maternal diet, can compromise, at critical periods of development, the neurovascular maturation of the offspring. Foetal exposure to maternal high-fat diet (mHFD), common to Western societies, has been shown to disturb neurovascular development in neonates and long-term permeability of the neurovasculature. Nevertheless, the effects of mHFD on the offspring’s cerebrovascular health remains largely elusive. Here, we sought to address this knowledge gap by using a translational mouse model of mHFD exposure. Three-dimensional and ultrastructure analysis of the neurovascular unit (vasculature and parenchymal cells) in mHFD-exposed offspring revealed major alterations of the neurovascular organization and metabolism. These alterations were accompanied by changes in the expression of genes involved in metabolism and immunity, indicating that neurovascular changes may result from abnormal brain metabolism and immune regulation. In addition, mHFD-exposed offspring showed persisting behavioural alterations reminiscent of neurodevelopmental disorders, specifically an increase in stereotyped and repetitive behaviours into adulthood.

Identifiable Dietary Patterns of Pregnant Women: A Canadian Sample

Purpose: To estimate the percentage of a sample of pregnant women in Canada following a vegetarian, vegan, low-carbohydrate, gluten-free, Mediterranean, or well-balanced diet, before and during pregnancy and to explore if pregnant women received and were satisfied with nutrition information received from health care providers (HCPs). Methods: Participants were conveniently sampled through Facebook and Twitter. An online survey collected data on sociodemographic characteristics, maternal diet, and whether women received and were satisfied with nutrition information from their HCPs. The McNemar test assessed changes in the proportion of diets followed before and during pregnancy. Results: Of 226 women, most followed a well-balanced diet before (76.9%) and during (72.9%) pregnancy (p = 0.26). Vegetarian, gluten-free, vegan, and low-carbohydrate diets were the least followed diets before and during pregnancy (vegetarian: 7.6% vs 5.3%; gluten-free: 4.9% vs 4.0%; vegan: 2.7% vs 2.2%; low-carbohydrate:4.0% vs 0.4%). Overall, the number of women following restrictive diets before pregnancy was significantly reduced throughout pregnancy (19.1% vs 12.0%, p < 0.001). Only 52.0% of women received nutrition information from their primary HCP, and 35.6% were satisfied with the nutrition information received. Conclusions: Most women followed a well-balanced diet before and during pregnancy and approximately one-third were satisfied with the information received from HCPs.

Decreasing the level of hemicelluloses in sow's lactation diet affects the milk composition and post-weaning performance of low birthweight piglets.

Hemicelluloses (HC) are polysaccharides constituents of the cell walls of plants. They are fermented in the gut to produce volatile fatty acids (VFA). The present study investigated the effects of decreasing HC level in sow's lactation diet on sow performances, offspring development and milk composition. From 110 days (d) of gestation until weaning (26±0.4 d post-farrowing), 40 Swiss Large White sows were assigned to one of the four dietary treatments: (1) T12 (HC: 120.6 g/kg), (2) T11 (HC: 107.6 g/kg), (3) T9 (HC: 86.4g/kg) and (4) T7 (HC: 71.9 g/kg). Milk was collected at 3 and 17d of lactation. At birth, piglets were divided into two groups according to their birthweight (BtW): normal (N-BtW; BtW > 1.20 kg) or low (L-BtW; BtW ≤ 1.20 kg). Decreased HC levels in the maternal diet linearly increased (P ≤ 0.05) the body weight of L-BtW piglets at two weeks post-weaning and linearly decreased (P ≤ 0.05) diarrhoea incidence and duration in this category. The concentrations of copper, threonine and VFA, as well as the proportion of butyrate, in milk linearly increased (P ≤ 0.05), whereas lactose content linearly decreased (P ≤ 0.05) with decreased HC in the maternal diet. The present study provides evidence that decreasing HC level in sow's lactation diet can positively affect the composition and VFA profile of milk and ultimately favour the growth and health of L-BtW piglets.

Maternal high-fat diet programs white and brown adipose tissue lipidome and transcriptome in offspring in a sex- and tissue-dependent manner in mice

Objective The prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring. Methods Mice dam were fed either a control diet or a high-fat diet (HFD) for 6-week prior mating and continued their respective diet during gestation and lactation. At weaning, female and male offspring were fed the HFD until sacrifice. White (WAT) and brown (BAT) adipose tissues were investigated in vivo by nuclear magnetic resonance at two different timepoints in life (midterm and endterm) and tissues were collected at endterm for lipidomic analysis and RNA sequencing. We explored the sex-dependent metabolic adaptation and gene programming changes by maternal HFD in visceral AT (VAT), subcutaneous AT (SAT) and BAT of offspring. Results We show that the triglyceride profile varies between adipose depots, sexes and maternal diet. In female offspring, maternal HFD remodels the triglycerides profile in SAT and BAT, and increases thermogenesis and cell differentiation in BAT, which may prevent metabolic complication later in life. Male offspring exhibit whitening of BAT and hyperplasia in VAT when born from high-fat mothers, with impaired metabolic profile. Maternal HFD differentially programs gene expression in WAT and BAT of female and male offspring. Conclusion Maternal HFD modulates metabolic profile in offspring in a sex-dependent manner. A sex- and maternal diet-dependent gene programming exists in VAT, SAT, and BAT which may be key player in the sexual dimorphism in the metabolic adaptation later in life.

Bacterial Gut Microbiota and Infections During Early Childhood

Gut microbiota composition during the first years of life is variable, dynamic and influenced by both prenatal and postnatal factors, such as maternal antibiotics administered during labor, delivery mode, maternal diet, breastfeeding, and/or antibiotic consumption during infancy. Furthermore, the microbiota displays bidirectional interactions with infectious agents, either through direct microbiota-microorganism interactions or indirectly through various stimuli of the host immune system. Here we review these interactions during childhood until 5 years of life, focusing on bacterial microbiota, the most common gastrointestinal and respiratory infections and two well characterized gastrointestinal diseases related to dysbiosis (necrotizing enterocolitis and Clostridioides difficile infection). To date, most peer-reviewed studies on the bacterial microbiota in childhood have been cross-sectional and have reported patterns of gut dysbiosis during infections as compared to healthy controls; prospective studies suggest that most children progressively return to a “healthy microbiota status” following infection. Animal models and/or studies focusing on specific preventive and therapeutic interventions, such as probiotic administration and fecal transplantation, support the role of the bacterial gut microbiota in modulating both enteric and respiratory infections. A more in depth understanding of the mechanisms involved in the establishment and maintenance of the early bacterial microbiota, focusing on specific components of the microbiota-immunity-infectious agent axis is necessary in order to better define potential preventive or therapeutic tools against significant infections in children.

Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences

The societal burden of non-communicable disease is closely linked with environmental exposures and lifestyle behaviours, including the adherence to a poor maternal diet from the earliest preimplantation period of the life course onwards. Epigenetic variations caused by a compromised maternal nutritional status can affect embryonic development. This review summarises the main epigenetic modifications in mammals, especially DNA methylation, histone modifications, and ncRNA. These epigenetic changes can compromise the health of the offspring later in life. We discuss different types of nutritional stressors in human and animal models, such as maternal undernutrition, seasonal diets, low-protein diet, high-fat diet, and synthetic folic acid supplement use, and how these nutritional exposures epigenetically affect target genes and their outcomes. In addition, we review the concept of thrifty genes during the preimplantation period, and some examples that relate to epigenetic change and diet. Finally, we discuss different examples of maternal diets, their effect on outcomes, and their relationship with assisted reproductive technology (ART), including their implications on epigenetic modifications.

Longitudinal dietary trajectories from preconception to mid-childhood in women and children in the Southampton Women’s Survey and their relation to offspring adiposity: a group-based trajectory modelling approach

Background Rates of childhood obesity are increasing globally, with poor dietary quality an important contributory factor. Evaluation of longitudinal diet quality across early life could identify timepoints and subgroups for nutritional interventions as part of effective public health strategies. Objective This research aimed to: (1) define latent classes of mother-offspring diet quality trajectories from pre-pregnancy to child age 8–9 years, (2) identify early life factors associated with these trajectories, and (3) describe the association between the trajectories and childhood adiposity outcomes. Design Dietary data from 2963 UK Southampton Women’s Survey mother-offspring dyads were analysed using group-based trajectory modelling of a diet quality index (DQI). Maternal diet was assessed pre-pregnancy and at 11- and 34-weeks’ gestation, and offspring diet at ages 6 and 12 months, 3, 6-7- and 8–9-years using interviewer-administered food frequency questionnaires. At each timepoint, a standardised DQI was derived using principal component analysis. Adiposity age 8–9 years was assessed using dual-energy X-ray absorptiometry (DXA) and BMI z-scores. Results A five-trajectory group model was identified as optimal. The diet quality trajectories were characterised as stable, horizontal lines and were categorised as poor (n = 142), poor-medium (n = 667), medium (n = 1146), medium-better (n = 818) and best (n = 163). A poorer dietary trajectory was associated with higher maternal pre-pregnancy BMI, smoking, multiparity, lower maternal age and lower educational attainment. Using linear regression adjusted for confounders, a 1-category decrease in the dietary trajectory was associated with higher DXA percentage body fat (0.08 SD (95% confidence interval 0.01, 0.15) and BMI z-score (0.08 SD (0.00, 0.16) in the 1216 children followed up at age 8–9 years. Conclusion Mother-offspring dietary trajectories are stable across early life, with poorer diet quality associated with maternal socio-demographic and other factors and childhood adiposity. The preconception period may be an important window to promote positive maternal dietary changes in order to improve childhood outcomes.