The significance of contact with microbes in early life for subsequent health has been the subject of intense research during the last 2 decades. Disturbances in the establishment of the indigenous intestinal microbiome caused by cesarean section delivery or antibiotic exposure in early life have been linked to the risk of immune-mediated and inflammatory conditions such as atopic disorders, inflammatory bowel disease and obesity later in life. Distinct microbial populations have recently been discovered at maternal sites including the amniotic cavity and breast milk, as well as meconium, which have previously been thought to be sterile. Our understanding of the impact of fetal microbial contact on health outcomes is still rudimentary. Breast milk is known to modulate immune and metabolic programming. The breast milk microbiome is hypothesized to guide infant gut colonization and is affected by maternal health status and mode of delivery. Immunomodulatory factors in breast milk interact with the maternal and infant gut microbiome and may mediate some of the health benefits associated with breastfeeding. The intimate connection between the mother and the fetus or the infant is a potential target for microbial therapeutic interventions aiming to support healthy microbial contact and protect against disease.

Early supplementation with oregano essential oil (EO) in milk replacer (MR) may improve growth, immune responses, the microbiota and the metabolome in dairy calves during pre-weaning and in adulthood. Sixteen female dairy calves (3 days of age) were divided in two groups (n = 8/group): the control group (no EO) and the EO group (0.23 ml of EO in MR during 45 days). After weaning, calves were kept in a feedlot and fed ad libitum. The animals were weighed, and blood and faecal samples were collected on days 3 (T0), 45 (T1) and 370 (T2) to measure the biochemical profile and characterise peripheral blood mononuclear cells (PBMCs; CD4+, CD8+, CD14+, CD21+ and WC1+), the metabolome and microbiota composition. The EO group only had greater average daily weight gain during the suckling (EO supplementation) period (P = 0.030). The EO group showed higher average CD14+ population (monocytes) values, a lower abundance of Ruminococcaceae UCG-014, Faecalibacterium, Blautia and Alloprevotella and increased abundances of Allistipes and Akkermansia. The modification of some metabolites in plasma, such as butyric acid, 3-indole-propionic acid and succinic acid, particularly at T1, are consistent with intestinal microbiota changes. The data suggest that early EO supplementation increases feed efficiency only during the suckling period with notable changes in the microbiota and plasma metabolome; however, not all of these changes can be considered desirable from a gut health point of view. Additional research studies is required to demonstrate that EOs are a viable natural alternative to antibiotics for improving calf growth performance and health.

Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler’s Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother−child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; −2.01 [−3.43, −0.59], p = 0.006), verbal composite (−1.93 [−3.33, −0.53], p = 0.007), and information scale (−0.41 [−0.70, −0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%–41% and 7%–22%, respectively, and accounted for approximately 5%–10% greater variation in male children’s cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.

Zinc is an important nutrient involved in cell division, physical growth, and immune system function. Most studies evaluating the nutritional status related to zinc and prematurity were conducted with hospitalized preterm infants. These studies show controversial results regarding the prevalence of deficiency, clinical implications, and the effect of zinc supplementation on mortality, infectious diseases, and growth in these groups. This study aimed to compare serum and erythrocyte zinc levels in a group of preterm and full-term infants after 9 months of age, and related the zinc levels to dietary intake and anthropometric indicators in both groups. This cross-sectional study compared 43 preterm infants (24 to 33 weeks) aged 9–24 months to 47 full-term healthy infants. Outcome measures: anthropometric indicators and dietary intake. Blood sample for serum and erythrocyte zinc levels (ICP-MS, Inductively Coupled Plasma Mass Spectrometry). There was no difference between the groups regarding the mean of serum and erythrocyte zinc. Variables associated with higher serum zinc levels were breastfeeding at evaluation (β = 20.11 µg/dL, 95% CI 9.62–30.60, p < 0.001) and the later introduction of solid foods (β = 6.6 µg/dL, 95% CI 5.3–11.4, p < 0.001). Breastfeeding was also associated with higher erythrocyte zinc levels. The zinc levels were adequate in both groups, there was no association with anthropometric indicators or dietary intake and were slightly influenced by breastfeeding and time of solid food introduction.

Breast milk constitutes one of the most important sources of postnatal microbes. However, the influence of perinatal factors on the milk microbiome is still poorly understood. The aim of our study was to assess the impact of mode of delivery on the microbiome composition and diversity present in breast milk of healthy mothers. Mature milk samples (n=10) were taken from mothers after 1 month of exclusively breastfeeding. Microbiomes from milk samples were analyzed with 16S ribosomal RNA gene pyrosequencing and targeted quantitative polymerase chain reaction (PCR). Despite inter-individual variability in bacterial composition, The Principal Coordinates Analysis clearly separated milk microbiome from mothers with vaginal delivery (n=6) from those who undergo C-section (n=4). In addition, higher bacterial diversity and richness was found in milk samples from vaginal deliveries. Quantitative PCR data showed that higher levels of Bifidobacterium spp. were related significantly to lower levels of Staphylococcus spp. Despite the low sample size, our data suggest that mode of delivery has an important impact on milk microbiome composition. Further studies with larger sample sizes are needed to confirm these results and to understand the biological effects of C-section associated microbes on infant’s health.

Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gut immunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for these variations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this study was to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilk International cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott Architect Analyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r=−0.49, P<0.001). Adjusting for maternal parity, smoking, fresh fruit and fish consumption and allergen sensitization, multiple regression model showed that IgA levels were influenced by colostrum collection time (P<0.0001) and country of collection (P<0.01). Mode of delivery influence did not appear to be significant in univariate comparisons, once adjusted for the above maternal characteristics it showed a significant influence on total IgA (P=0.01). We conclude that the concentration of IgA in colostrum drops rapidly after birth and future studies should always consider this factor in analysis. IgA concentration varied significantly between countries, with the highest level detected in Moscow and lowest in Verona. Mode of delivery effect should be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find the cause of variations in IgA levels between the countries.

Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, P<0.01 and 22.19 v. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (β-coefficient, 0.37, P<0.05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre/postnatal exposures may affect gut immunity and risk of allergic disease.

Although bariatric surgery is approved for a woman of child-bearing age with an interest in subsequent pregnancy, reports of in utero growth issues during pregnancy have garnered a closer look at the impact of maternal surgical weight loss on the pre- and postpartum periods. Offspring of dams having received vertical sleeve gastrectomy (VSG) are born small-for-gestational age and have increased risk for metabolic syndrome later in life. Here, we aimed to determine whether the postnatal catch-up growth trajectory of bariatric offspring may be affected by milk composition. Milk samples were collected at postnatal day 15/16 from dams having received VSG surgery and fed a high-fat diet (HFD) (H-VSG), Sham surgery and fed chow (C-Sham), or Sham surgery and fed HFD (H-Sham). Milk obtained from H-VSG dams had elevated glucose (P < 0.05) and significantly reduced triglyceride content (P < 0.01). Milk from H-Sham dams had the lowest amount of milk protein (P < 0.05). Fatty acid composition measured by fractionation was largely not affected by surgery but rather maternal diet. No difference was observed in milk leptin levels; however, insulin, adiponectin, and growth hormone levels were significantly increased in milk from H-VSG animals. H-Sham had the lowest level of immunoglobulin (Ig)A, whereas IgG was significantly reduced in H-VSG. Taken together, the quality of milk from H-VSG dams suggests that milk composition could be a factor in reducing the rate of growth during the lactation period.

Insulin-like growth factor 1 (IGF1) is a regulator of human growth during infancy and childhood, known to promote bone and muscle growth as well as lipid accumulation. This study aimed to investigate the effects of formula milk with or without IGF1 supplementation (in the form of pure IGF1 or bovine colostrum) on growth and body composition in infant cynomolgus macaques during the first 6 months of life. Three groups of infants were nursery-reared and received formula milk with or without IGF1 or bovine colostrum supplementation for 4 months, and a fourth group consisting of breast-fed infants was included for comparison (n=6 for each group). Ranked-based analysis of covariance was used to detect differences between adjusted means for sex. No differences in weight, height, fat mass, and fat-free mass could be detected between groups. However, bone mineral density (BMD) was significantly different between groups at the end of formula feeding. Infants that received bovine colostrum supplementation displayed higher mean BMD than infants of all other groups, with no differences between the latter three groups. In conclusion, our results suggest that supplementation with bovine colostrum can enhance BMD in formula-fed infants, an effect that apparently does not depend on IGF1. Bovine colostrum supplementation could be beneficial for long-term bone health in infants with suboptimal bone growth.

The human microbiome plays a number of critical roles in host physiology. Evidence from longitudinal cohort studies and animal models strongly supports the theory that maldevelopment of the microbiome in early life can programme later-life disease. The early-life microbiome develops in a clear stepwise manner over the first 3 years of life. During this highly dynamic time, insults such as antibiotic use and formula feeding can adversely affect the composition and temporal development of the microbiome. Such experiences predispose infants for the development of chronic health conditions later in life. This review highlights key factors that disrupt the early-life microbiome and highlights major non-communicable diseases which are underpinned by early-life dysbiosis.

The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.

Approximately 10% of all babies worldwide are born preterm, and preterm birth is the leading cause of perinatal mortality in developed countries. Although preterm birth is associated with adverse short- and long-term health outcomes, it is not yet clear whether this relationship is causal. Rather, there is evidence that reduced foetal growth, preterm birth and the long-term health effects of both of these may all arise from a suboptimal intrauterine environment. Further, most infants born preterm also experience suboptimal postnatal growth, with potential adverse effects on long-term health and development. A number of interventions are used widely in the neonatal period to optimise postnatal growth and development. These commonly include supplementation with macronutrients and/or micronutrients, all of which have potential short-term risks and benefits for the preterm infant, whereas the long-term health consequences are largely unknown. Importantly, more rapid postnatal growth trajectory (and the interventions required to achieve this) may result in improved neurological outcomes at the expense of increased cardiovascular risk in later life.

Adiponectin and leptin are involved in appetite control and body weight regulation. We aimed to evaluate the relationship between breast milk adipokine levels and short-term growth of preterm and term infants. Thirty-one preterm (median=35.3 weeks) and 34 term (median=38.7 weeks) infants were enrolled. Enzyme-linked immunosorbent assay was used to detect adipokines in mature milk. Infant growth was followed during the first 3 months. Although weight gain in the first month was insufficient, positive linear growth was observed in the following months for preterm infants, while term infants had positive steady linear growth. The median level of adipokines was found to be higher in preterm infants (P>0.05). Adiponectin showed significant negative correlations with some anthropometric measurements of term infants. However, in preterm infants, adiponectin was negatively correlated with length increment and positively correlated with body mass index (BMI) increment in the second–third month. In addition, leptin was negatively associated with the head circumference at birth in preterm infants and the triceps skinfold thickness increment in the first–second month term infants (P<0.05). In linear regression models, while gestational age, adiponectin and leptin were not related, maternal age and pre-pregnancy BMI had effects on body weight increment in 0–1 months (P<0.05). In conclusion, adiponectin may affect short-term growth, while leptin has no important effect. It would be beneficial to carry out longitudinal studies to evaluate the effects of these adipokines on the growth of infants.

Understanding the role and importance of nutrition in early postnatal life, as an influence on lifelong vulnerability to poor health, is an important part of current research. We need to be able to define optimal patterns of infant feeding, not just to support growth and development in infancy, but also as determinants of later health. To date, much of the focus on the long-term effects of infant nutrition has been on milk feeding, to compare breast and formula feeding and to evaluate the effects of exclusivity, timing and duration of feeding different types of milk in infancy; other aspects of infant feeding such as age at introduction of solid foods and type of weaning diet have received less attention, and relatively little is known about their links to later health. Contemporary data are needed to enable us to move beyond explanation of historical infant feeding data in order to understand and predict health outcomes in future generations. Ongoing and new population studies, that include infants from diverse settings, will be key to providing generalizable data that can be used to define optimal feeding practice. There are some methodological challenges ahead, although significant progress has already been made, and further progress is envisaged in the future. In particular, the opportunity to bring together epidemiological studies and new mechanistic insights that will help identify key aspects of infant nutrition and their causal effects offer great promise both in moving this field forward as well as the potential for health benefits for future generations.

Obesity and its complications occur at alarming rates worldwide. Epidemiological data have associated perinatal conditions, such as malnutrition, with the development of some disorders, such as obesity, dyslipidemia, diabetes, and cardiovascular diseases, in childhood and adulthood. Exclusive breastfeeding has been associated with protection against long-term chronic diseases. However, in humans, the interruption of breastfeeding before the recommended period of 6 months is a common practice and can increase the risk of several metabolic disturbances. Nutritional and environmental changes within a critical window of development, such as pregnancy and breastfeeding, can induce permanent changes in metabolism through epigenetic mechanisms, leading to diseases later in life via a phenomenon known as programming or developmental plasticity. However, little is known regarding the underlying mechanisms by which precocious weaning can result in adipose tissue dysfunction and endocrine profile alterations. Here, the authors give a comprehensive report of the different animal models of early weaning and programming that can result in the development of metabolic syndrome. In rats, for example, pharmacological and nonpharmacological early weaning models are associated with the development of overweight and visceral fat accumulation, leptin and insulin resistance, and neuroendocrine and hepatic changes in adult progeny. Sex-related differences seem to influence this phenotype. Therefore, precocious weaning seems to be obesogenic for offspring. A better understanding of this condition seems essential to reducing the risk for diseases. Additionally, this knowledge can generate new insights into therapeutic strategies for obesity management, improving health outcomes.

Evidence suggests that breastfeeding during infancy lowers the risk of metabolic syndrome (MS) and its attendant risk factors in adult life. To investigate the influence of feeding type on the risk factors of MS, we assessed insulin sensitivity and lipid and apolipoprotein metabolism in preterm infants. Blood samples were collected from preterm infants at the time of discharge. Infants were separated into two groups: a breast milk (BM) group receiving ⩾90% of their intake from BM, and a mixed-fed (MF) group receiving ⩾50% of their intake from formula. The following indices were then compared between the two groups. Blood glucose and serum insulin levels were used to calculate the quantitative insulin sensitivity check index (QUICKI). We also measured serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels, and the ratios of TC/HDLc, LDLc/HDLc and apoB/apoA1. The mean gestational age was 32.9 weeks at birth, and blood samples were collected at a mean corrected age of 37.4 weeks. There were 22 infants in the BM group and 19 in the MF group. QUICKI was significantly higher in the BM group. TC, HDLc and apoA1 were not significantly different between the groups, but LDLc and apoB levels were significantly higher in the BM group. The TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were significantly higher in the BM group. In preterm infants, the type of feeding exposure in the early postnatal period may influence glucose, lipid and apolipoprotein metabolism, and affect markers of MS.

Environmental factors during perinatal life can lead to changes in the mammary gland, making it susceptible to cancer in adulthood. Breastfeeding has a special importance since it takes place at a critical period of growth and development of the newborn. We aimed to analyze if an appropriate lactation protects the offspring against mammary carcinogenesis during adult life and explore the mechanisms involved in the protective effect. One-day-old Sprague-Dawley female rats were randomly distributed in litters of three (L3), eight (L8) or 12 (L12) pups per dam, to induce a differential consumption of breast milk. At 55 days of age, the animals were treated with a single dose of dimethylbenzanthracene to study tumor latency, incidence and progression. Histological, immunohistochemical and Western blot studies were performed. We observed lower incidence and higher latency in L3 compared to the other groups. The mitotic index and expression of proliferating cell nuclear antigen (PCNA) was significantly augmented in tumors of L12 rats compared to L3 and L8, while the apoptotic index was augmented in tumors of L3 v. L12. Cleaved caspase 8 was significantly higher in tumors from L3 compared to L12. Tumors developed in L3 have a greater number of apoptotic bodies and a greater expression of caspase 8. These results demonstrate that the animals that maintained a higher intake of maternal milk (L3) presented lower incidence and greater tumor latency. Lower consumption of breast milk (L12) would increase tumor mitosis and the expression of PCNA, explaining the higher tumor incidence observed in this group.

Literature describes breast milk as the best food for the newborn, recommending exclusive breastfeeding for up to 6 months of age. However, it is not available for more than 40% of children worldwide. Pharmacological and non-pharmacological models of 3-day early weaning were developed in rodents to investigate later outcomes related solely to this nutritional insult. Thus, the present work aimed to describe biometric, nutritional, biochemical, and cardiovascular outcomes in adult male rats submitted to 3-day early weaning achieved by maternal deprivation. This experimental model comprises not only nutritional insult but also emotional stress, simulating mother abandoning. Male offspring were physically separated from their mothers at 21st (control) or 18th (early weaning) postnatal day, receiving water/food ad libitum. Analysis performed at postnatal days 30, 90, 150, and 365 encompassed body mass and food intake monitoring and serum biochemistry determination. Further assessments included hemodynamic, echocardiographic, and cardiorespiratory evaluation. Early-weaned males presented higher body weight when compared to control as well as dyslipidemia, higher blood pressure, diastolic dysfunction, and cardiac hypertrophy in adult life. Animals early deprived of their mothers have also presented a worse performance on the maximal effort ergometer test. This work shows that 3-day early maternal deprivation favors the development of cardiovascular disease in male rats.

Maternal milk consumption can cause changes in the mammary epithelium of the offspring that result in the expression of molecules involved in the induction of differentiation, reducing the risk of developing mammary cancer later in life. We previously showed that animals that maintained a higher intake of maternal milk had a lower incidence of mammary cancer. In the present study, we evaluated one of the possible mechanisms by which the consumption of maternal milk could modify the susceptibility to mammary carcinogenesis. We used Sprague Dawley rats reared in litters of 3 (L3), 8 (L8), or 12 (L12) pups per mother in order to generate a differential consumption of milk. Whole mounts of mammary glands were performed to analyze the changes in morphology. Using real-time polymerase chain reaction (PCR), we analyzed the expression of mammary Pinc, Tbx3, Stat6, and Gata3 genes. We use the real-time methylation-specific polymerase chain reaction method to assess the methylation status of Stat6 and Gata3 CpG sites. Our findings show an increase in the size of the epithelial tree and a smaller number of ducts called terminal end buds in L3 vs. L12. We observed an increased expression of mRNA of Stat6, Gata3, Tbx3, and a lower expression of Pinc in L3 with respect to L12. Stat6 and Gata3 are more methylated in the CpG islands of the promoter analyzed in L12 vs. L3. In conclusion, the increased consumption of maternal milk during the postnatal stage generates epigenetic and morphological changes associated with the differentiation of the mammary gland.