Does Maternal Diet Influence Future Infant Taste and Odor Preferences? A Critical Analysis.

The dietary choices a mother makes during pregnancy offer her developing fetus its earliest exposure to the family's culinary preferences. This comprehensive literature review synthesizes five decades of research, which has provided valuable insights into fetal flavor learning. Converging evidence across various species supports the functionality of fetal chemoreceptive systems by the end of gestation, enabling the detection of an extensive array of chemosensory cues derived from the maternal diet and transmitted to the amniotic fluid. The fetus effectively encodes these flavors, resulting in their enhanced acceptance after birth. While existing studies predominantly concentrate on fetal learning about odor volatiles, limited evidence suggests a capacity for learning about gustatory (i.e., taste) properties. Examining whether these prenatal odor, taste, and flavor experiences translate into enduring shifts in dietary behaviors beyond weaning remains a crucial avenue for further investigation.

Effects of pregnancy and lactation prebiotics supplementation on infant allergic disease: A randomized controlled trial.

BACKGROUND: Ingestion of prebiotics during pregnancy and lactation may have immunomodulatory benefits for the developing fetal and infant immune system and provide a potential dietary strategy to reduce the risk of allergic diseases. OBJECTIVE: We sought to determine whether maternal supplementation with dietary prebiotics reduces the risk of allergic outcomes in infants with hereditary risk. METHODS: We undertook a double-blind randomized controlled trial in which pregnant women were allocated to consume prebiotics (14.2 g daily of galacto-oligosaccharides and fructo-oligosaccharides in the ratio 9:1) or placebo (8.7 g daily of maltodextrin) powder from less than 21 weeks' gestation until 6 months postnatal during lactation. Eligible women had infants with a first-degree relative with a history of medically diagnosed allergic disease. The primary outcome was medically diagnosed infant eczema by age 1 year, and secondary outcomes included allergen sensitization, food allergy, and recurrent wheeze by age 1 year. RESULTS: A total of 652 women were randomized between June 2016 and November 2021 (329 in the prebiotics group and 323 in the placebo group). There was no significant difference between groups in the percentage of infants with medically diagnosed eczema by age 1 year (prebiotics 31.5% [103 of 327 infants] vs placebo 32.6% [105 of 322 infants]; adjusted relative risk, 0.98; 95% CI, 0.77-1.23; P = .84). Secondary outcomes and safety measures also did not significantly differ between groups. CONCLUSIONS: We found little evidence that maternal prebiotics supplementation during pregnancy and lactation reduces the risk of medically diagnosed infant eczema by age 1 year in infants who are at hereditary risk of allergic disease.

Maternal diet during gestation affect prostatic tissue component in SHR/Izm offspring.

BACKGROUND: Numerous studies have investigated the associations between maternal nutritional status and various diseases, with the underlying mechanism often attributed to epigenetic changes. However, limited research has been conducted on the relationship between maternal nutrition and benign prostatic hyperplasia (BPH). In this study, we aimed to explore the potential association between maternal nutrition and BPH using an animal experiment and evaluating the findings through fluorescent immunostaining and genetic analysis. METHODS: Female spontaneously hypertensive rats (SHR/Izm) were randomly assigned to three groups at the start of pregnancy: a standard diet group (SD; 17% protein, 7% fat), a low-protein diet group (LPD; 6% protein, 7% fat), and a high-fat diet group (HFD; 22% protein, 35% fat). The diets were maintained throughout gestation. After giving birth, both the mothers and their pups were exclusively fed a standard diet. Male pups were euthanized at 48 weeks, and their prostates were removed. The composition of the ventral prostate (VP) was evaluated using fluorescent immunostaining with antibodies for cytokeratin, vimentin, and Ki-67. Microarray analysis, real-time RT-PCR, and DNA methylation analysis using pyrosequencing were performed. Statistical analysis was conducted using one-way ANOVA and Tukey's multiple comparison test, with a significance level set at p < 0.05. RESULTS: Pups in the LPD group exhibited significant underweight from birth (1 day; SD vs. LPD vs. HFD: 4.46 vs. 4.08 vs. 4.35, p = 0.04) until weaning (21 days; SD vs. LPD vs. HFD: 30.8 vs. 27.4 vs. 29.2, p = 0.03). However, they exhibited catch-up growth, and there was no significant difference at 48 weeks (p = 0.84). The epithelial area in the ventral prostate was significantly increased in the LPD group (SD vs. LPD vs. HFD: 39% vs. 48% vs. 37%, p = 0.01), while the stromal area was significantly increased in the HFD group (SD vs. LPD vs. HFD: 11% vs. 11% vs. 15%, p < 0.01). Gene ontology analysis of the gene expression microarray showed increased activity in developmental processes (SD vs. LPD: p = 6.3E-03, SD vs. HFD: p = 7.2E-03), anatomical structure development (SD vs. LPD: p = 6.3E-03, SD vs. HFD: p = 5.3E-03), and cell differentiation (SD vs. LPD: p = 0.018, SD vs. HFD: p = 0.041) in both the LPD and HFD groups. Real-time RT-PCR revealed high expression levels of the transcription factors NFκB (p < 0.01) and Smad3 (p < 0.01) in both the LPD and HFD groups. XIAP, an apoptosis inhibitor, was increased in the LPD group (p = 0.02). The TGF beta pathway, associated with epithelial mesenchymal transition (EMT), and vimentin (p < 0.01) were upregulated in the HFD group. Pyrosequencing DNA methylation analysis of the TGF beta pathway indicated hypomethylation of TGFb1, TGFbR1, and Smad3 in all groups, although there were no significant differences. CONCLUSIONS: Our findings suggest that both maternal undernutrition and obesity influence the prostatic development of offspring. Maternal consumption of a low protein diet promotes epithelial hyperplasia through the upregulation of apoptosis inhibitors, while a high fat diet leads to increased stromal growth through the induction of EMT.

Maternal n-3 enriched diet reprograms the offspring neurovascular transcriptome and blunts inflammation induced by endotoxin in the neonate.

Infection during the perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) transforms brain lipid composition in the offspring and protects the neonatal brain from stroke, in part by blunting injurious immune responses. Critical to the interface between the brain and systemic circulation is the vasculature, endothelial cells in particular, that support brain homeostasis and provide a barrier to systemic infection. Here, we examined whether maternal PUFA-enriched diets exert reprograming of endothelial cell signalling in postnatal day 9 mice after modeling aspects of infection using LPS. Transcriptome analysis was performed on microvessels isolated from brains of pups from dams maintained on 3 different maternal diets from gestation day 1: standard, n-3 enriched or n-6 enriched diets. Depending on the diet, in endothelial cells LPS produced distinct regulation of pathways related to immune response, cell cycle, extracellular matrix, and angiogenesis. N-3 PUFA diet enabled higher immune reactivity in brain vasculature, while preventing imbalance of cell cycle regulation and extracellular matrix cascades that accompanied inflammatory response in standard diet. Cytokine analysis revealed a blunted LPS response in blood and brain of offspring from dams on n-3 enriched diet. Analysis of cerebral vasculature in offspring in vivo revealed no differences in vessel density. However, vessel complexity was decreased in response to LPS at 72 h in standard and n-6 diets. Thus, LPS modulates specific transcriptomic changes in brain vessels of offspring rather than major structural vessel characteristics during early life. N-3 PUFA-enriched maternal diet in part prevents an imbalance in homeostatic processes, alters inflammation and ultimately mitigates changes to the complexity of surface vessel networks that result from infection. Importantly, maternal diet may presage offspring neurovascular outcomes later in life.

Periconceptional maternal diet quality and offspring wheeze trajectories: Japan Environment and Children's Study.

BACKGROUND: The role of prenatal diet on childhood wheezing and subsequent risk of asthma is inconclusive, which may be partly due to the heterogeneity in wheezing phenotypes. We aimed to identify wheeze trajectories in early childhood and to examine their associations with periconceptional maternal diet quality. METHODS: Data from 70,530 mother-child pairs of liveborn singletons from the Japan Environment and Children's Study were analysed. Wheezing was reported by caregivers using a modified International Study of Asthma and Allergies in Childhood questionnaire yearly from 1 to 4 years of age, from which trajectories were derived using group-based trajectory modelling. Maternal diet in the year preceding the first trimester of pregnancy was assessed using a validated food frequency questionnaire; overall diet quality was determined using the balanced diet score based on the Japanese Food Guide Spinning Top. Bayesian inference of multinomial logistic regression models was performed to examine the association between maternal diet quality and wheeze trajectory in early childhood. RESULTS: We identified four wheeze trajectories: 'never/infrequent' (69.1%; reference group), 'early-childhood onset' (6.2%), 'transient early' (16.5%) and 'persistent' (8.2%). After adjustment for confounders, a higher quartile of maternal balanced diet score was associated with a lower risk of belonging to the 'transient early' and 'persistent' wheeze trajectories compared with the 'never/infrequent' wheeze trajectory by 10% of both. Maternal balanced diet score was not associated with belonging to the 'early-childhood onset' wheeze trajectory. CONCLUSION: Improving maternal diet quality prior to conception may reduce certain wheeze phenotypes in early childhood.

Higher maternal bread and thiamine intakes are associated with increased infant allergic disease.

BACKGROUND: A mother's diet during pregnancy may influence her infant's immune development. However, as potential interactions between components of our dietary intakes can make any nutritional analysis complex, here we took a multi-component dietary analysis approach. METHODS: Nutritional intake data was collected from 639 pregnant women using a validated semi-quantitative food frequency questionnaire to reflect their dietary intakes during 32-36 weeks of gestation. To investigate their dietary intake pattern, we calculated Dietary Inflammatory Index scores. Maternal consumption of 12 food groups, 20 individual whole foods, and 18 specific nutrient intakes, along with any vitamin and mineral supplementation, were determined. Infant outcomes included eczema, allergen sensitization, and IgE-mediated food allergy. Regression-based analyses with covariates adjustment were applied. RESULTS: Women with higher white bread consumption were more likely to have an infant with doctor-diagnosed eczema (adjusted relative risk [aRR] 1.16; 95% CI 1.08, 1.24; p < .001) and IgE-mediated food allergy (aRR 1.14; 95% CI 1.02, 1.28; p = .02). Higher maternal intakes of fiber-rich bread (aRR 1.14; 95% CI 1.04, 1.25; p = .01) and legumes (aRR 1.11; 95% CI 1.02, 1.21; p = .02) were also associated with infant doctor-diagnosed eczema. Higher maternal thiamine intakes were associated with increased parent-reported infant eczema (aRR 1.08; 95% CI 1.03, 1.12; p < .001). CONCLUSION: In Australia, where bread flour is fortified with thiamine, we identified consistent links between higher maternal thiamine-rich diets and increased risk of infant eczema and food allergy. Our results highlight a need for further investigation of potential effects of high thiamine exposures on immune development, especially in-utero.

Carotenoids in maternal and cord blood, breast milk and their association with maternal dietary intake: a longitudinal study in Shanghai, China.

Carotenoids are important bioactive substances in breast milk, the profile of which is seldom studied. This study aimed to explore the profile of carotenoids in breast milk and maternal/cord plasma of healthy mother-neonate pairs in Shanghai, China, and their correlation with dietary intake. Maternal blood, umbilical cord blood and breast milk samples from five lactation stages (colostrum, transitional milk and early-, mid- and late-term mature milk) were collected. Carotenoid levels were analysed by HPLC. Carotenoid levels in breast milk changed as lactation progressed (P < 0·001). ß-Carotene was the primary carotenoid in colostrum. Lutein accounted for approximately 50 % of total carotenoids in transitional milk, mature milk and cord blood. Positive correlations were observed between five carotenoids in umbilical cord blood and maternal blood (P all < 0·001). ß-Carotene levels were also correlated between maternal plasma and three stages of breast milk (r = 0·605, P < 0·001; r = 0·456, P = 0·011, r = 0·446; P = 0·013, respectively). Dietary carotenoid intakes of lactating mothers also differed across lactation stages, although no correlation with breast milk concentrations was found. These findings suggest the importance of exploring the transport mechanism of carotenoids between mothers and infants and help guide the development of formulas for Chinese infants as well as the nutritional diets of lactating mothers.

Maternal dietary intervention during lactation impacts the maternal faecal and human milk microbiota.

AIMS: To determine the effect of a two-week reduced fat and sugar and increased fibre maternal dietary intervention on the maternal faecal and human milk (HM) microbiomes. METHODS AND RESULTS: Faecal swabs and HM samples were collected from mothers (n = 11) immediately pre-intervention, immediately post-intervention, and 4 and 8 weeks post-intervention, and were analysed using full-length 16S rRNA gene sequencing. Maternal macronutrient intake was assessed at baseline and during the intervention. Maternal fat and sugar intake during the intervention were significantly lower than pre-intervention (P = <0.001, 0.005, respectively). Significant changes in the bacterial composition of maternal faeces were detected after the dietary intervention, with decreases in the relative abundance of Bacteroides caccae (P = <0.001) and increases in the relative abundance of Faecalibacillus intestinalis (P = 0.006). In HM, the diet resulted in a significant increase in Cutibacterium acnes (P = 0.001) and a decrease in Haemophilus parainfluenzae (P = <0.001). The effect of the diet continued after the intervention, with faecal swabs and HM samples taken 4 and 8 weeks after the diet showing significant differences compared to baseline. CONCLUSION: This pilot study demonstrates that short-term changes in maternal diet during lactation can alter the bacterial composition of the maternal faeces and HM.

Effects of maternal supplementation with DHA and/or egg yolk powder on monoamine homeostasis in the perinatal piglet brain.

OBJECTIVES: Reports indicate that children of mothers who received docosahexaenoic acid (DHA) or egg yolk supplements during pregnancy have improved performance on cognitive tasks and brain growth; their combination has recently been demonstrated to modulate functional neuronal network connectivity in the human-relevant piglet brain. To expand upon this functional connectivity analysis, neurochemical evaluation to determine how dietary supplementation with one or both of these nutrients during the last trimester of pregnancy alters monoamine homeostasis in selected brain regions of piglets was done. METHODS: Beginning gestation days 60-69 through weaning, pregnant sows were fed either control diet or diets supplemented with egg yolk powder, DHA, or both. Brains were then collected, and monoamine neurotransmitters and their metabolites were quantified from various brain regions with HPLC-ECD. RESULTS: Relative to controls, egg yolk supplementation increased serotonin metabolite (5-HIAA) levels in the cerebellum, while DHA supplementation decreased serotonin (5-HT) levels in the prefrontal cortex; combined supplementation increased norepinephrine metabolite (MHPG) levels in the prefrontal cortex and cerebellum, but decreased 5-HT levels in the posterior hippocampus. Notably, all diets increased serotonin, dopamine, and their respective metabolite levels in the substantia nigra. DISSCUSSION: This suggests both overlapping and specific effects of DHA and components of egg yolk in the context of maternal supplementation during pregnancy and lactation that might facilitate optimal neurodevelopment, with the nigrostriatal pathway being particularly sensitive. Such supplementations might impact brain function and facilitate development later in life through modulating monoamine homeostasis.

Processed foods and diet quality in pregnancy may affect child neurodevelopment disorders: a narrative review.

OBJECTIVE: To review the evidence on the association between maternal exposure to ultra-processed food (UPF) categories, UPF diet items, and overall diet quality, as assessed by recognized dietary indices, and neurodevelopmental outcomes in offspring. METHODS: PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Scholar databases were searched for original articles on female gestational exposure to UPF categories, individual elements of the UPF diet, or indices of diet quality, in relation to outcomes regarding their offspring's neurocognitive development, according to neuropsychometric and behavioral scales, anthropometric/psychomotor indices, and symptoms/diagnosis of neurodevelopmental disorders (NDDs). RESULTS: Fourteen articles were selected and underwent the quantitative analysis. Six of these examined diet quality, and eight exposure to UPF categories or specific UPF foods. The maternal population was adult (18+). Child cognitive development was negatively impacted by a diet featuring many processed foods, saturated fats, and sugars. Conversely, a Med-diet led to better neurodevelopment, particularly verbal intelligence and executive functions, in middle childhood. DISCUSSION: A maternal diet with many UPFs, saturated fats, and total sugars (especially those added or hidden in packaged carbonated beverages) can adversely affect a child's cognitive development. Knowledge needs to be further extended and managed from a prevention perspective in light of the well-known negative effects of UPFs on human health in all age groups.

Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p.

BACKGROUNDS: The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs. RESULTS: In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development. CONCLUSION: These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-ß-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development.

The microbiome in pregnancy and early life-Highlights from the 11th Maria Delivoria-Papadopoulos Perinatal Symposium.

This review was based on a symposium that examined novel aspects of the microbiome during pregnancy and early life and explored papers published by the lecturers. For example, it showed that bacterial extracellular vesicles derived from the microbiome harboured in various maternal niches, carried bacterial deoxyribonucleic acid, were isolated from the placenta and may have confounded placental microbiome studies. Maternal diet was responsible for the composition and diversity of breast milk microbiota, and may have shaped the offspring's microbiome and influenced their immune components. Probiotics and antibiotics administered perinatally may have had beneficial but also long-lasting adverse effects on offspring.

Nutritional Intake in Dichorionic Twin Pregnancies: A Descriptive Analysis of a Multisite United States Cohort.

INTRODUCTION: Twin gestations have greater nutritional demands than singleton gestations, yet dietary intakes of women with twin gestations have not been well described. METHODS: In a prospective, multi-site US study of 148 women with dichorionic twin gestations (2012-2013), we examined longitudinal changes in diet across pregnancy. Women completed a food frequency questionnaire during each trimester of pregnancy. We examined changes in means of total energy and energy-adjusted dietary components using linear mixed effects models. RESULTS: Mean energy intake (95% CI) across the three trimesters was 2010 kcal/day (1846, 2175), 2177 kcal/day (2005, 2349), 2253 kcal/day (2056, 2450), respectively (P = 0.01), whereas the Healthy Eating Index-2010 was 63.9 (62.1, 65.6), 64.5 (62.6, 66.3), 63.2 (61.1, 65.3), respectively (P = 0.53). DISCUSSION: Women with twin gestations moderately increased total energy as pregnancy progressed, though dietary composition and quality remained unchanged. These findings highlight aspects of nutritional intake that may need to be improved among women carrying twins.

The influence of maternal diet on offspring's gut microbiota in early life.

BACKGROUND: The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. OBJECTIVE: In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved in maternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. CONCLUSION: The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood.

Maternal caffeine intake during pregnancy and the risk of delivering a small for gestational age baby: Kuopio Birth Cohort.

PURPOSE: High caffeine intake during pregnancy is associated with restricted fetal growth. We aimed to evaluate the association between maternal caffeine intake during early and late pregnancy and the risk of delivering a small for gestational age (SGA) baby. METHODS: Kuopio Birth Cohort (KuBiCo) is a prospective cohort study including women whose pregnancies and deliveries were treated at the prenatal clinics in outpatient healthcare centers and in Kuopio University Hospital, Finland. Maternal diet and caffeine intake during the first (n = 2007) and third (n = 4362) trimester of pregnancy were assessed using a 160-item food frequency questionnaire (2013-2022). SGA was defined as birth weight corrected for gestational age below - 2 standard deviations from the mean, according to the sex-specific Finnish fetal growth curves. RESULTS: Altogether in 32 and 38% (1st and 3rd trimester) of all women and in 44 and 52% of coffee drinkers, caffeine intake exceeded the recommendation for caffeine intake ( ≤ 200 mg/day) during pregnancy. The women with moderate (51-200 mg/day) (aOR 1.87; 95% CI: 1.16-3.02) and high (> 200 mg/day) (aOR 1.51; 95% CI: 1.08-2.10) caffeine intake during the first trimester were in the highest risk of having an SGA newborn. Caffeine intake in the third trimester of pregnancy was not associated with SGA. CONCLUSIONS: Moderate and high caffeine intake during early pregnancy is associated with SGA. As the results suggest that even moderate caffeine intake during the first trimester may increase the risk of SGA, the intake within recommendation limits does not necessarily appear to be safe for pregnant women and their newborns.

A Comprehensive Assessment of the Environmental Impact of Different Infant Feeding Types: The Observational Study GREEN MOTHER.

AIM(S): To observe and compare the environmental impacts of different types of infant feeding, considering the use of formula, infant feeding accessories, potentially increased maternal dietary intake during breastfeeding (BF) and food consumption habits. DESIGN: An observational cross-sectional multicentre study conducted in the Barcelona Metropolitan Area of the Catalan Institute of Health. METHODS: Data were collected from 419 postpartum women on infant feeding type (formula milk and accessories), maternal dietary intake (24-h register) and food consumption habits from November 2022 to April 2023. The environmental impacts (climate change (CC), water consumption and water scarcity) of the infant feeding types and maternal diet were calculated using the IPCC, ReCiPE and AWARE indicators, respectively. The differences in impacts were calculated by Kruskal-Wallis test. RESULTS: Significant differences for the three environmental impacts were observed. The CC impact of formula milk and feeding accessories was 0.01 kg CO2eq for exclusive BF, 1.55 kg CO2eq for mixed feeding and 4.98 kg CO2eq for formula feeding. While BF mothers consumed an extra 238 kcal, no significant differences were found related to maternal diet across feeding types. CONCLUSION: Exclusive BF was the most sustainable type of infant feeding, considering formula and infant feeding accessories. In our study, the difference between the impacts of BF and non-BF mothers' diet was insignificant. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Offer informative and educational support for midwives and other healthcare professionals on BF and a healthy, sustainable diet to transfer this knowledge to the general public. IMPACT: Raise the general public's awareness about BF and a healthy, sustainable diet. To reduce environmental impacts through behavioural changes. REPORTING METHOD: STROBE. PATIENT OR PUBLIC CONTRIBUTION: Patients of the Catalan Health Service reviewed the content of the data collection tools. TRIAL REGISTRATION: (for the whole GREEN MOTHER project): NCT05729581 (https://clinicaltrials.gov).

Sex-Specific Changes to Brain Fatty Acids, Plasmalogen, and Plasma Endocannabinoids in Offspring Exposed to Maternal and Postnatal High-Linoleic-Acid Diets.

Linoleic acid (LA) is required for neuronal development. We have previously demonstrated sex-specific changes in cardiovascular and hepatic function in rat offspring from mothers consuming a high-LA diet, with some effects associated with reduced LA concentration in the postnatal diet. At this time, the impact of a high-maternal-LA diet on offspring brain development and the potential for the postnatal diet to alter any adverse changes are unknown. Rat offspring from mothers fed low- (LLA) or high-LA (HLA) diets during pregnancy and lactation were weaned at postnatal day 25 (PN25) and fed LLA or HLA diets until sacrifice in adulthood (PN180). In the offspring's brains, the postnatal HLA diet increased docosapentaenoate in males. The maternal HLA diet increased LA, arachidonate, docosapentaenoate, C18:0 dimethylacetal (DMA), C16:0 DMA, C16:0 DMA/C16:0, and C18:0 DMA/C18:0, but decreased eoicosenoate, nervoniate, lignocerate, and oleate in males. Maternal and postnatal HLA diets reduced oleate and vaccenate and had an interaction effect on myristate, palmitoleate, and eicosapentaenoate in males. In females, maternal HLA diet increased eicosadienoate. Postnatal HLA diet increased stearate and docosapentaenoate. Maternal and postnatal HLA diets had an interaction effect on oleate, arachidate, and docosahexaenoic acid (DHA)/omega (n)-6 docosapentaenoic acid (DPA) in females. Postnatal HLA diet decreased DHA/n-6 DPA in males and females. Postnatal HLA diet increased plasma endocannabinoids (arachidonoyl ethanolamide and 2-arachidonoyl glycerol), as well as other N-acyl ethanolamides and testosterone. HLA diet alters brain fatty acids, plasma endocannabinoids, and plasmalogen concentrations in a development-specific and sex-specific manner.

The Effect of Maternal High-Fat or High-Carbohydrate Diet during Pregnancy and Lactation on Cytochrome P450 2D (CYP2D) in the Liver and Brain of Rat Offspring.

Cytochrome P450 2D (CYP2D) is important in psychopharmacology as it is engaged in the metabolism of drugs, neurosteroids and neurotransmitters. An unbalanced maternal diet during pregnancy and lactation can cause neurodevelopmental abnormalities and increases the offspring's predisposition to neuropsychiatric diseases. The aim of the present study was to evaluate the effect of maternal modified types of diet: a high-fat diet (HFD) and high-carbohydrate diet (HCD) during pregnancy and lactation on CYP2D in the liver and brain of male offspring at 28 (adolescent) or 63 postnatal days (young adult). The CYP2D activity and protein level were measured in the liver microsomes and the levels of mRNAs of CYP2D1, 2D2 and 2D4 were investigated both in the liver and brain. In the liver, both HFD and HCD increased the mRNA levels of all the three investigated CYP2D genes in adolescents, but an opposite effect was observed in young adults. The CYP2D protein level increased in adolescents but not in young adults. In contrast, young adults showed significantly decreased CYP2D activity. Similar effect of HFD on the CYP2D mRNAs was observed in the prefrontal cortex, while the effect of HCD was largely different than in the liver (the CYP2D2 expression was not affected, the CYP2D4 expression was decreased in young adults). In conclusion, modified maternal diets influence the expression of individual CYP2D1, CYP2D2 and CYP2D4 genes in the liver and brain of male offspring, which may affect the metabolism of CYP2D endogenous substrates and drugs and alter susceptibility to brain diseases and pharmacotherapy outcome.

Early-life dietary exposures mediate persistent shifts in the gut microbiome and visceral fat metabolism.

In utero dietary exposures are linked to the development of metabolic syndrome in adult offspring. These dietary exposures can potentially impact gut microbial composition and offspring metabolic health. Female BALB/c mice were administered a lard, lard + flaxseed oil, high sugar, or control diet 4 wk before mating, throughout mating, pregnancy, and lactation. Female offspring were offered low-fat control diet at weaning. Fecal 16S sequencing was performed. Untargeted metabolomics was performed on visceral adipose tissue (VAT) of adult female offspring. Immunohistochemistry was used to determine adipocyte size, VAT collagen deposition, and macrophage content. Hippurate was administered via weekly intraperitoneal injections to low-fat and high-fat diet-fed female mice and VAT fibrosis and collagen 1A (COL1A) were assessed by immunohistochemistry. Lard diet exposure was associated with elevated body and VAT weight and dysregulated glucose metabolism. Lard + flaxseed oil attenuated these effects. Lard diet exposures were associated with increased adipocyte diameter and VAT macrophage count. Lard + flaxseed oil reduced adipocyte diameter and fibrosis compared with the lard diet. Hippurate-associated bacteria were influenced by lard versus lard + flax exposures that persisted to adulthood. VAT hippurate was increased in lard + flaxseed oil compared with lard diet. Hippurate supplementation mitigated VAT fibrosis pathology. Maternal high-fat lard diet consumption resulted in long-term metabolic and gut microbiome programming in offspring, impacting VAT inflammation and fibrosis, and was associated with reduced VAT hippurate content. These traits were not observed in maternal high-fat lard + flaxseed oil diet-exposed offspring. Hippurate supplementation reduced VAT fibrosis. These data suggest that detrimental effects of early-life high-fat lard diet exposure can be attenuated by dietary omega-3 polyunsaturated fatty acid supplementation.

Perinatal high-fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility.

Perinatal high-fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical anti-stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments, cerebrospinal fluid extraction, in vivo recordings of gastric tone, motility and gastric emptying rates, and in vitro electrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN-DMV inputs and dysregulates vagal brain-gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVNOXT neurons that project to the DMV, but increased PVNCRF neurons. Both in vitro electrophysiology recordings of DMV neurons and in vivo recordings of gastric motility and tone demonstrated that, following pHFD, PVNCRF -DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress. KEY POINTS: Maternal high-fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspring. The present study demonstrates that perinatal high-fat diet exposure downregulates hypothalamic-vagal oxytocin (OXT) inputs but upregulates hypothalamic-vagal corticotropin releasing factor (CRF) inputs. Both in vitro and in vivo studies demonstrated that, following perinatal high-fat diet, CRF receptors were tonically active at NTS-DMV synapses, and that pharmacological antagonism of these receptors restored the appropriate gastric response to OXT. The current study suggests that perinatal high-fat diet exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress.