Associations between Dietary Sugar and Fiber with Infant Gut Microbiome Colonization at 6 Mo of Age.

BACKGROUND: The taxonomic composition of the gut microbiome undergoes rapid development during the first 2-3 y of life. Poor diet during complementary feeding has been associated with alterations in infant growth and compromised bone, immune system, and neurodevelopment, but how it may affect gut microbial composition is unknown. OBJECTIVES: This cross-sectional study aimed to examine the associations between early-life nutrition and the developing infant gut microbiota at 6 mo of age. METHODS: Latino mother-infant pairs from the Mother's Milk Study (n = 105) were included. Infant gut microbiota and dietary intake were analyzed at 6 mo of age using 16S ribosomal RNA amplicon sequencing and 24-h dietary recalls, respectively. Poisson generalized linear regression analysis was performed to examine associations between dietary nutrients and microbial community abundance while adjusting for infants' mode of delivery, antibiotics, infant feeding type, time of introduction of solid foods, energy intake, and body weight. A P value of <0.05 was used to determine the statistical significance in the study. RESULTS: Infants with higher consumption of total sugar exhibited a lower relative abundance of the genera Bacteroides (ß = -0.01; 95% CI: -0.02, -0.00; P = 0.03) and genus Clostridium belonging to the Lachnospiraceae family (ß = -0.02; 95% CI: -0.03, -0.00; P = 0.01). In addition, a higher intake of free sugar (which excludes sugar from milk, dairy, and whole fruit) was associated with several bacteria at the genus level, including Parabacteroides genus (ß = 0.03; 95% CI: 0.01, 0.05; P = 0.001). Total insoluble fiber intake was associated with favorable bacteria at the genus level such as Faecalibacterium (ß = 0.28; 95% CI: 0.03, 0.52; P = 0.02) and Coprococcus (ß = 0.28; 95% CI: 0.02, 0.52; P = 0.03). CONCLUSION: These findings demonstrate that early-life dietary intake at 6 mo impacts the developing gut microbiome associated with the presence of both unfavorable gut microbes and dietary fiber-associated commensal microbes.

Babies, Bugs, and Barriers: Dietary Modulation of Intestinal Barrier Function in Early Life.

The intestinal barrier is essential in early life to prevent infection, inflammation, and food allergies. It consists of microbiota, a mucus layer, an epithelial layer, and the immune system. Microbial metabolites, the mucus, antimicrobial peptides, and secretory immunoglobulin A (sIgA) protect the intestinal mucosa against infection. The complex interplay between these functionalities of the intestinal barrier is crucial in early life by supporting homeostasis, development of the intestinal immune system, and long-term gut health. Exclusive breastfeeding is highly recommended during the first 6 months. When breastfeeding is not possible, milk-based infant formulas are a safe alternative. Breast milk contains many bioactive components that help to establish the intestinal microbiota and influence the development of the intestinal epithelium and the immune system. Importantly, breastfeeding lowers the risk for intestinal and respiratory tract infections. Here we review all aspects of intestinal barrier function and the nutritional components that impact its functionality in early life, such asmicronutrients, bioactive milk proteins, milk lipids, and human milk oligosaccharides. These components are present in breast milk and can be added to milk-based infant formulas to support gut health and immunity.

Mitochondrial dysfunction and epigenetics underlying the link between early-life nutrition and non-alcoholic fatty liver disease.

Early-life malnutrition plays a critical role in foetal development and predisposes to metabolic diseases later in life, according to the concept of 'developmental programming'. Different types of early nutritional imbalance, including undernutrition, overnutrition and micronutrient deficiency, have been related to long-term metabolic disorders. Accumulating evidence has demonstrated that disturbances in nutrition during the period of preconception, pregnancy and primary infancy can affect mitochondrial function and epigenetic mechanisms. Moreover, even though multiple mechanisms underlying non-alcoholic fatty liver disease (NAFLD) have been described, in the past years, special attention has been given to mitochondrial dysfunction and epigenetic alterations. Mitochondria play a key role in cellular metabolic functions. Dysfunctional mitochondria contribute to oxidative stress, insulin resistance and inflammation. Epigenetic mechanisms have been related to alterations in genes involved in lipid metabolism, fibrogenesis, inflammation and tumorigenesis. In accordance, studies have reported that mitochondrial dysfunction and epigenetics linked to early-life nutrition can be important contributing factors in the pathogenesis of NAFLD. In this review, we summarise the current understanding of the interplay between mitochondrial dysfunction, epigenetics and nutrition during early life, which is relevant to developmental programming of NAFLD.

Supplementation of n-3 PUFAs in Adulthood Attenuated Susceptibility to Pentylenetetrazol Induced Epilepsy in Mice Fed with n-3 PUFAs Deficient Diet in Early Life.

The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.

Improving complementary feeding practice and child growth in Indonesia through family empowerment intervention.

Objectives: This study aimed to evaluate the effectiveness of family empowerment intervention in improving complementary feeding practices and child growth in Indonesia. METHODS: A quasi-experimental design was used to gather data from 60 mothers and their youngest children, aged 6-11 months, who participated in this project from two urban areas in Surabaya, East Java, Indonesia. The independent variable was an eleven-week family empowerment intervention, including pre- and post-test. The dependent variable was complementary feeding practice and child growth. Complementary feeding practice indicators consist of minimum dietary diversity (MDD), meal frequency (MMF), acceptable diet (MAD), energy, protein, and zinc adequacy, assessed using a 3x24 hour food recall. Child growth indicators consist of weight-for-age (WAZ), length/height-for-age (HAZ), and weight-for-length/height (WHZ) measured using an infantometer and baby scales. The data obtained were then analysed using the McNemar test, the Wilcoxon Signed-Rank test, and the Mann Whitney U test, with a significance level of a<0.05. RESULTS: Family empowerment intervention significantly improved complementary feeding practice indicators, including MDD, MMF, MAD, energy, protein, and zinc adequacy. It also significantly increased the child's WAZ, HAZ, and WHZ scores (p<0.05). CONCLUSIONS: The family empowerment intervention can be used as a nursing intervention to improve a family's ability to provide appropriate complementary feeding practices and support a child's optimal growth.

Early Childhood Lutein and Zeaxanthin Intake Is Positively Associated with Early Childhood Receptive Vocabulary and Mid-Childhood Executive Function But No Other Cognitive or Behavioral Outcomes in Project Viva.

BACKGROUND: Lutein and zeaxanthin are carotenoids associated with better cognition in older adults. Recent evidence suggests that their dietary intake may also have cognitive implications in childhood. OBJECTIVE: The aim was to examine associations of early childhood lutein and zeaxanthin (L/Z) intake with cognition in early and mid-childhood. METHODS: Among 1378 children in Project Viva, a prospective cohort, mothers reported their child's dietary intake in early childhood (median: 3.2 y) using a food-frequency questionnaire. Child cognition and behavior were assessed at the same time point using the Peabody Picture Vocabulary Test (PPVT-III) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) and at mid-childhood (median: 7.7 y) using the Kaufman Brief Intelligence Test, the WRAVMA drawing subtest, the Wide Range Assessment of Memory and Learning, the Behavior Rating Inventory of Executive Function (BRIEF), and the Strengths and Difficulties Questionnaire. RESULTS: Children consumed a daily mean (SD) of 1.0 (0.4) mg L/Z in early childhood. Children in the third-quartile category of L/Z intake had a mean PPVT-III score 2.40 (95% CI: 0.27, 4.53) points higher than children in the lowest quartile category in early childhood, suggesting better receptive vocabulary. Children in the highest quartile category of L/Z intake had a parent-reported mean BRIEF Global Executive Composite score 1.65 (95% CI: -3.27, -0.03) points lower than children in the lowest quartile category in mid-childhood, indicating better executive function. We did not observe associations between L/Z intake and any of the other cognitive or behavioral outcomes assessed. CONCLUSIONS: The overall findings do not provide strong evidence of an association between child L/Z intake and cognition and behavior. However, the positive associations found between early childhood L/Z intake and early childhood receptive vocabulary and mid-childhood executive function, in addition to previous evidence of neurodevelopmental benefit of L/Z intake, suggest that this relation deserves further investigation.

Neighborhood Disadvantage, Greenness, and Population Density as Predictors of Breastfeeding Practices: A Population Cohort Study from Finland.

BACKGROUND: Many environmental factors are known to hinder breastfeeding, yet the role of the family living environment in this regard is still poorly understood. OBJECTIVES: We used data from a large cohort to identify associations between neighborhood characteristics and breastfeeding behavior. METHODS: Our observational study included 11,038 children (0-2 years) from the Southwest Finland Birth Cohort. Participant information was obtained from the Medical Birth Register and municipal follow-up clinics. Neighborhood socioeconomic disadvantage, greenness, and population density were measured for a period of 5 years prior to childbirth within the residential neighborhood on a 250 × 250-m grid. Any breastfeeding and breastfeeding at 6 months were the primary outcomes. Binary logistic regression models were adjusted for maternal health and socioeconomic factors. RESULTS: Adjusted analyses suggest that mothers living in less populated areas were less likely to display any breastfeeding (OR: 0.46; 95% CI: 0.36, 0.59) and breastfeeding at 6 months (OR: 0.37; 95% CI: 0.34, 0.40). Mothers living in highly disadvantaged neighborhoods were less likely to display any breastfeeding if the neighborhood was less populated (OR: 0.54; 95% CI: 0.30, 0.95) but more likely to breastfeed at 6 months if the neighborhood was highly populated (OR: 3.74; 95% CI: 1.92, 7.29). Low greenness was associated with higher likelihood of any breastfeeding (OR: 3.82; 95% CI: 1.53, 9.55) and breastfeeding at 6 months (OR: 4.41; 95% CI: 3.44, 5). CONCLUSIONS: Our results suggest that neighborhood characteristics are associated with breastfeeding behavior in Finland. Unravelling breastfeeding decisions linked to the living environment could help identify interventions that will allow the appropriate support for all mothers and infants across different environmental challenges.

Maternal Intake of Lutein and Zeaxanthin during Pregnancy Is Positively Associated with Offspring Verbal Intelligence and Behavior Regulation in Mid-Childhood in the Project Viva Cohort.

BACKGROUND: Lutein and zeaxanthin are carotenoids associated with better cognition at older age. To our knowledge, no previous study has evaluated their cognitive implications in the prenatal period, when the brain undergoes its most rapid development. OBJECTIVE: The objective of this study was to examine associations of maternal lutein and zeaxanthin (L/Z) intake during pregnancy with child cognition. DESIGN: Among 1580 mother-child pairs in Project Viva, a prospective cohort, we assessed maternal intake of L/Z during pregnancy using food frequency questionnaires and offspring cognition by the Visual Recognition Memory paradigm in infancy, the Peabody Picture Vocabulary Test and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) in early childhood, and the Kaufman Brief Intelligence Test (KBIT-II), the WRAVMA drawing subtest, and the Wide Range Assessment of Memory and Learning in mid-childhood. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Strengths and Difficulties Questionnaire. RESULTS: Mothers consumed a daily mean (SD) of 2.6 (2.0) mg L/Z in the first and second trimesters of pregnancy. Mean mid-childhood KBIT-II verbal scores were higher with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: 2.67 (95% CI: 0.13, 5.20) and for second trimester: 3.55 (95% CI: 0.81, 6.28)], indicating better verbal intelligence. Secondary analyses on cognitive subtests showed that mean mid-childhood BRIEF Behavioral Regulation Index scores were lower with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: -1.63 (95% CI: -3.22, -0.04) and for second trimester: -1.89 (95% CI: -3.58, -0.21)], indicating better behavior regulation ability. CONCLUSIONS: Higher maternal L/Z intake during pregnancy was associated with better offspring verbal intelligence and behavior regulation ability in mid-childhood, suggesting a potential benefit during prenatal development. We did not find a benefit of higher maternal L/Z intake on other child cognitive or behavioral outcomes. Project Viva is registered at clinicaltrials.gov as NCT02820402.

Exploring healthcare professionals' views of the acceptability of delivering interventions to promote healthy infant feeding practices within primary care: a qualitative interview study.

OBJECTIVE: Early-life nutrition plays a key role in establishing healthy lifestyles and preventing chronic disease. This study aimed to (1) explore healthcare professionals' (HCP) opinions on the acceptability of and factors influencing the delivery of interventions to promote healthy infant feeding behaviours within primary care and (2) identify proposed barriers/enablers to delivering such interventions during vaccination visits, to inform the development of a childhood obesity prevention intervention. DESIGN: A qualitative study design was employed using semi-structured telephone interviews. Data were analysed using qualitative content analysis; findings were also mapped to the Theoretical Framework of Acceptability (TFA). SETTING: Primary care in Ireland. PARTICIPANTS: Twenty-one primary care-based HCP: five practice nurses, seven general practitioners, three public health nurses, three community dietitians and three community medical officers. RESULTS: The acceptability of delivering interventions to promote healthy infant feeding within primary care is influenced by the availability of resources, HCP's roles and priorities, and factors relating to communication and relationships between HCP and parents. Proposed barriers and enablers to delivering interventions within vaccination visits include time constraints v. opportunistic access, existing relationships and trust between parents and practice nurses, and potential communication issues. Barriers/enablers mapped to TFA constructs of Affective Attitude, Perceived Effectiveness and Self-Efficacy. CONCLUSIONS: This study provides a valuable insight into HCP perspectives of delivering prevention-focused infant feeding interventions within primary care settings. While promising, factors such as coordination and clarity of HCP roles and resource allocation need to be addressed to ensure acceptability of interventions to HCP involved in delivery.

Differing planes of pre- and postweaning phase nutrition in Holstein heifers: II. Effects on circulating leptin, luteinizing hormone, and age at puberty.

The objectives were to investigate the effects of differing planes of pre- and postweaning nutrition on prepubertal serum leptin concentrations, LH profiles, and age at puberty in Holstein heifers. Thirty-six Holstein calves were randomly assigned to either a low (5 L) or high (10 L of whole milk/d) preweaning plane of nutrition from 1 to 7 wk of age, a transition diet (a dry total mixed ration with 85% of concentrate) from wk 8 to 10, and to either a low (70%) or high (85% of concentrate dry total mixed ration) postweaning plane from 11 to 25 wk of age. Serum leptin concentrations were measured every 2 wk from 1 to 25 wk of age, and LH profiles were determined both at wk 15 and 25 based on sequential blood samples taken every 12 min over 10 h. Starting at 26 wk of age, ovaries were examined weekly by transrectal ultrasonography until first ovulation (puberty) was confirmed. Heifers that received the high preweaning plane diet had greater mean (± standard error; SE) leptin concentrations during the preweaning phase than those fed the low plane (2.9 ± 0.1 vs. 2.6 ± 0.1 ng/mL). During the postweaning phase, mean circulating leptin was greater in heifers fed the high compared with the low postweaning diet [3.2 ng/mL (95% confidence interval; CI = 2.7 to 3.4) vs. 2.5 ng/mL (95% CI = 2.3 to 2.8)]. Mean (± SE) amplitude (2.1 ± 0.1 vs. 1.7 ± 0.1 ng/mL), peak (2.2 ± 0.1 vs. 1.8 ± 0.1 ng/mL), and duration (35.6 ± 2.1 vs. 28.7 ± 2.0 min) of LH pulses assessed at wk 15 were greater in heifers offered the high than those offered the low preweaning plane, but no nutritional effects were observed on LH pulses at wk 25. Mean (± SE) age at puberty was 250 ± 9 d and was not influenced by planes of nutrition. However, the likelihood of attaining puberty by 30 wk of age was greater (hazard ratio = 3.8; 95% CI = 1.0 to 14.4) in heifers fed the high postweaning plane compared with the low plane. Heifers achieving puberty by 30 wk also had greater leptin concentrations from wk 1 to 25, whereas for every 1 ng/mL increase in circulating leptin at wk 15 and 25, days to puberty were estimated to decrease by 22 d (95% CI = 1 to 44) and 13 d (95% CI = 1 to 24), respectively. Increasing the preweaning plane from 5 to 10 L/d of whole milk increased serum leptin concentrations at wk 1, 3, and 5 and LH pulse amplitude, peak, and duration at wk 15. Increasing the postweaning plane from 70 to 85% of concentrate resulted in greater circulating leptin concentrations, which may be linked to an earlier onset of puberty.

Melatonin in Early Nutrition: Long-Term Effects on Cardiovascular System.

Breastfeeding protects against adverse cardiovascular outcomes in the long term. Melatonin is an active molecule that is present in the breast milk produced at night beginning in the first stages of lactation. This indoleamine appears to be a relevant contributor to the benefits of breast milk because it can affect infant health in several ways. The melatonin concentration in breast milk varies in a circadian pattern, making breast milk a chrononutrient. The consumption of melatonin can induce the first circadian stimulation in the infant's body at an age when his/her own circadian machinery is not functioning yet. This molecule is also a powerful antioxidant with the ability to act on infant cells directly as a scavenger and indirectly by lowering oxidant molecule production and enhancing the antioxidant capacity of the body. Melatonin also participates in regulating inflammation. Furthermore, melatonin can participate in shaping the gut microbiota composition, richness, and variation over time, also modulating which molecules are absorbed by the host. In all these ways, melatonin from breast milk influences weight gain in infants, limiting the development of obesity and comorbidities in the long term, and it can help shape the ideal cellular environment for the development of the infant's cardiovascular system.

Maternal gestational diabetes and infant feeding, nutrition and growth: a systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) is a major health problem, with increased risks of obesity and diabetes in offspring. However, little is known about the effect of GDM on infant feeding, nutrition and growth, and whether these factors play a role in mediating these risks. We systematically reviewed evidence for the effect of GDM on infant feeding, nutrition and growth. We searched MEDLINE, Web-of-Science, Embase, CINAHL and CENTRAL for studies that reported outcomes in infants <2 years who were and were not exposed to GDM. Studies of pre-gestational diabetes were excluded. Meta-analysis was performed for three epochs (1­6, 7­12, 13­24 months), using inverse-variance, fixed-effects methods. Primary outcomes were energy intake (kJ) and BMI (kg/m2). Twenty-five studies and 308 455 infants were included. Infants exposed to GDM, compared with those not exposed, had similar BMI at age 1­6 months (standardised mean difference (SMD) = 0·01, 95 % CI −0·04, 0·06; P = 0·69) and 7­12 months (SMD = 0·04, 95 % CI −0·01, 0·10; P = 0·09), reduced length at 1­6 and 7­12 months, increased whole-body fat at 1­6 months, higher rates of formula supplementation in hospital, shorter duration of breast-feeding and decreased rates of continued breast-feeding at 12 months. Breast milk of women with GDM had lower protein content. There was no association between GDM and infant weight and skinfold thickness. No data were available for nutritional intake and outcomes at 13­24 months. Low- or very low-quality evidence suggests GDM is not associated with altered BMI in infancy, but is associated with increased fat mass, high rates of formula use and decreased duration of breast-feeding.

Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring.

Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P < 0·05). The thymic cortico-medullar ratio was lower in adult offspring exposed to mLPD (P < 0·05). At PND180, the protein expression of the lymphotoxin ß receptor (P < 0·05), the autoimmune regulator (P < 0·05) and Forkhead Box P3 (FoxP3; P < 0·05) was all significantly lower in the mLPD group. The CD4+:CD8+ single-positive thymocyte subpopulation ratio and CD4+:CD8+ lymphocyte subpopulation ratio were increased in the mLPD group (P < 0·05). Among CD3+ lymphocytes, the proportions of CD4+CD8+ double-positive lymphocytes, CD31+ recent thymic emigrants and CD4+FoxP3+ lymphocytes were not significantly different between mLPD and control groups. These findings suggest mLPD during gestation induced long-lasting alterations in the development of thymic structure and thymic cell maturation and selection process in adult male rat offspring.

Early-life food nutrition, microbiota maturation and immune development shape life-long health.

The current knowledge about early-life nutrition and environmental factors that affect the interaction between the symbiotic microbiota and the host immune system has demonstrated novel regulatory target for treating allergic diseases, autoimmune disorders and metabolic syndrome. Various kinds of food nutrients (such as dietary fiber, starch, polyphenols and proteins) can provide energy resources for both intestinal microbiota and the host. The indigestible food components are fermented by the indigenous gut microbiota to produce diverse metabolites, including short-chain fatty acids, bile acids and trimethylamine-N-oxide, which can regulate the host metabolized physiology, immunity homeostasis and health state. Therefore it is commonly believed early-life perturbation of the microbial community structure and the dietary nutrition interference on the child mucosal immunity contribute to the whole life susceptibility to chronic diseases. In all, the combined interrelationship between food ingredients nutrition, intestinal microbiota configurations and host system immunity provides new therapeutic targets to treat various kinds of pathogenic inflammations and chronic diseases.

Association between early introduction of fruit juice during infancy and childhood consumption of sweet-tasting foods and beverages among children exposed and unexposed to gestational diabetes mellitus in utero.

BACKGROUND: Children exposed to gestational diabetes mellitus (GDM) in utero are at high-risk of obesity. Given that nutritional habits can track from infancy to childhood, the aim of this study was to evaluate the association between the timing of fruit juice introduction in infancy and later consumption of sweet-tasting foods and beverages among children exposed (GDM+) and unexposed (GDM-) to GDM. METHODS: A total of 107 GDM+ and 59 GDM- participated in the project. Data on the timing of fruit juice introduction during infancy were retrospectively collected for 62 GDM+ and 32 GDM- children. Current dietary intakes were collected with two 24-hour dietary recall questionnaires. Children were divided into groups according to the median timing of juice introduction (9 months). RESULTS: Mean age of children was 6.3 ± 2.6 and 7.6 ± 3.7 years for GDM+ and GDM- children, respectively (p = 0.08). Mean age of fruit juice introduction was similar between groups (p > 0.05). Consuming >1 serving of fruit juice per day was 2.72 times more prevalent among GDM+ children introduced to fruit juice <9 months, compared to GDM+ children introduced ≥9 months (CI: 1.19-6.20). This association was not observed in the GDM- group. The timing of fruit juice introduction was not associated with later consumption of sweets, desserts and sweet-tasting beverages when adjustment for children's age was made among GDM+ and GDM- children. CONCLUSION: Early introduction of fruit juice in infant diet is associated with higher prevalence of consumption of >1 serving of fruit juice per day in GDM+ children.

Preclinical Models of Altered Early Life Nutrition and Development of Reproductive Disorders in Female Offspring.

Early epidemiology studies in humans have and continue to offer valuable insight into the Developmental Origins of Health and Disease (DOHaD) hypothesis, which emphasises the importance of early-life nutritional and environmental changes on the increased risk of metabolic and reproductive disease in later life. Human studies are limited and constrained by a range of factors which do not apply to preclinical research. Animal models therefore offer a unique opportunity to fully investigate the mechanisms associated with developmental programming, helping to elucidate the developmental processes which influence reproductive diseases, and highlight potential biomarkers which can be translated back to the human condition. This review covers the use and limitations of a number of animal models frequently utilised in developmental programming investigations, with an emphasis on dietary manipulations which can lead to reproductive dysfunction in offspring.

Breastfeeding, Polyunsaturated Fatty Acid Levels in Colostrum and Child Intelligence Quotient at Age 5-6 Years.

OBJECTIVE: To examine the relationship of polyunsaturated fatty acid (PUFA) in breast milk with children's IQ. STUDY DESIGN: In the French Etude des Déterminants pré- et postnatals précoces du développement et de la santé de l'Enfant (EDEN) mother-child cohort, colostrum samples were collected at the maternity unit. Colostrum omega-6 and omega-3 PUFA were analyzed by gas chromatography. At age 5-6 years, the IQs of 1080 children were assessed using the Wechsler Preschool and Primary Scale of Intelligence-III. The relationships of breastfeeding duration and PUFA levels with children's IQs were examined by linear regression. RESULTS: Full scale IQ of ever breastfed children was 4.5 (95% CI: 2.7, 6.2) higher than never breastfed children in the unadjusted model, but this was not statistically significant in the adjusted model (1.3 points higher [-0.4, 3.0]). Any breastfeeding duration was associated with full scale (0.20 [0.00, 0.41] points/month) and verbal (0.31 [0.09, 0.52]) IQ. Colostrum linoleic acid (LA) levels were negatively associated with Verbal IQ (-0.6 [-1.1, 0.0] points per 1% level increase). Children exposed to colostrum high in LA and low in docosahexaenoic acid (DHA) had lower IQs than those exposed to colostrum high in DHA (3.0 [0.5, 5.5] points) and those exposed to colostrum low in LA and DHA (4.4 [1.6, 7.3] points). Finally, the association between breastfeeding duration and child IQ was stronger when LA levels were high. CONCLUSIONS: Duration of breastfeeding and colostrum PUFA levels were associated with children's IQs in the EDEN cohort. These data support breastfeeding and add evidence for the role of early PUFA exposure on childhood cognition.

Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming.

Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed "developmental programming" as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However, as with the use of GH in the clinical setting of short stature and GH-deficiency, the benefits of treatment are also, in some cases, associated with potential unwanted side effects that need to be taken into account before effective translation as an intervention modality in the DOHaD context can be undertaken.

The Impact of Timing of Introduction of Solids on Infant Body Mass Index.

OBJECTIVES: To evaluate the associations between breastfeeding duration, age at solids introduction, and their interaction in relation to infant (age 9-15 months) above normal body mass index (BMI). STUDY DESIGN: Cross-sectional, population-based study with 3153 infants from Melbourne (2007-2011). Above normal BMI (z score > 2, equivalent to >97.7th percentile) defined using the World Health Organization standard. RESULTS: Both longer duration of full and any (full or partial) breastfeeding were associated with lower odds of above normal BMI (eg, aOR, 0.37 [95% CI, 0.22-0.60] for full breastfeeding 4-5 months versus 0-1 months). Compared with introduction of solids at 5-6 months, both early and delayed introduction were associated with increased odds of above normal BMI (aOR for 4 months, 1.75 [95% CI, 1.10-2.80] and for ≥7 months, 2.64 [95% CI, 1.26-5.54] versus 6 months). Such associations differ by breastfeeding status at 4 months (interaction P = .08). Early introduction of solids was associated with increased odds of above normal BMI in both infants fully or partially breastfed for ≥4 months (aOR, 3.66; 95% CI, 1.41-9.51) and those breastfed for <4 months (aOR, 3.11; 95% CI, 1.39-6.97). Introduction of solids at ≥7 months was associated with increased odds of above normal BMI (aOR, 5.79; 95% CI, 1.91-17.49) among infants breastfed for <4 months only. CONCLUSION: Introduction of solids at 5-6 months, compared with either early or delayed introduction, is associated with decreased odds of above normal BMI at 1 year of age, regardless of infants' breastfeeding status at 4 months. These results may have implications for public health guidelines with regard to recommendations about the optimal timing of the introduction of solid foods in infancy.

Immune-Microbiota Interactions: Dysbiosis as a Global Health Issue.

Throughout evolution, microbial genes and metabolites have become integral to virtually all aspects of host physiology, metabolism and even behaviour. New technologies are revealing sophisticated ways in which microbial communities interface with the immune system, and how modern environmental changes may be contributing to the rapid rise of inflammatory noncommunicable diseases (NCDs) through declining biodiversity. The implications of the microbiome extend to virtually every branch of medicine, biopsychosocial and environmental sciences. Similarly, the impact of changes at the immune-microbiota interface are directly relevant to broader discussions concerning rapid urbanization, antibiotics, agricultural practices, environmental pollutants, highly processed foods/beverages and socioeconomic disparities--all implicated in the NCD pandemic. Here, we make the argument that dysbiosis (life in distress) is ongoing at a micro- and macro-scale and that as a central conduit of health and disease, the immune system and its interface with microbiota is a critical target in overcoming the health challenges of the twenty-first century.