Lidewij Schipper

While breastfeeding duration has been positively associated with later cognitive outcomes in childhood, behavioral assessments commonly used in early infancy may lack the sensitivity required to detect subtle differences. This study examined whether eye‐tracking during infancy can be used to detect differences in attentional development related to infant feeding practices in a generally well‐nourished population. Specifically, using data from the YOUth Baby & Child cohort ( N = 2647) collected in Utrecht, the Netherlands, infant attentional disengagement was assessed around 5 months (4–6 months) and around 10 months (9–11 months) of age, alongside child receptive vocabulary around 3 years (2–4 years) and around 6 years (5–7 years) of age. While a positive association was established between breastfeeding duration and receptive vocabulary around 6 years of age, no association was established between breastfeeding duration and attentional disengagement at either timepoint. These findings suggest that effects of early‐life nutrition on cognitive development in well‐nourished infants do not extend to early attentional development or are too subtle to be picked up using eye‐tracking. Future research could explore populations with greater developmental variability.

The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed “nutritional programming.” Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.

Semi-synthetic and grain-based diets are common rodent diets for biomedical research. Both diet types are considered nutritionally adequate to support breeding, growth, and long life, yet there are fundamental differences between them that may affect metabolic processes. We have characterized the effects of diet type on breeding outcomes, metabolic phenotype, and microbiota profile in adult mice. Healthy 8-week-old female and male C57BL/6J mice were fed a semi-synthetic or a grain-based diet for 12 weeks and changes in body weight and body composition were monitored. Breeding outcomes were determined. Body fat accumulation of female mice was lower on the semi-synthetic diet than on the grain-based diet. Pregnancy rate and newborn pup survival appeared to be lower in mice exposed to semi-synthetic diet compared to grain-based diet. Both female and male mice showed a profound change in fecal microbiota alpha and beta diversity depending on diet type. Our study shows that type of rodent diet may affect breeding outcomes whilst influencing metabolism and health of female laboratory mice. These factors have the potential to influence other experimental outcomes and the results suggest that semi-synthetic and grain-based diets are not interchangeable in research using rodent models. Careful consideration and increased understanding of the consequences of diet choice would lead to improvements in experimental design and reproducibility of study results.

Background: Lactose, a disaccharide of glucose and galactose, is the primary carbohydrate found in milk. Recently, there has been an increased demand for low lactose/lactose-free infant formulas. Maltodextrin (MDX) is a popular, alternative carbohydrate source in these formulas, yet the (long-term) health effects of consuming maltodextrin in early life are unclear. Previously, consuming galactose (partly replacing glucose) in a postweaning diet was shown to improve metabolic health in mice. Objective: To investigate the effects of partly replacing MDX with galactose in post-weaning diets on body composition and energy metabolism. Methods: Weaned, individually housed female C57BL/6JRccHsd mice received isocaloric diets (in a dough ball format) with different carbohydrate profiles for three weeks (postnatal day (PN)21-PN42). GLUGAL (lactose mimic, n = 13) contained 15.7 en% glucose, 15.7 en% galactose and 14.9 en% MDX, and GAL (n = 12) contained 15.7 en% galactose, no glucose and 30.6 en% MDX. MDX (n = 13) contained 38.4 en% MDX and 7.9 en% glucose. Energy metabolism was assessed via indirect calorimetry from PN40-PN42. At PN42, all mice were challenged with a 40 en% high-fat diet (HFD) until PN105. Body composition was measured weekly using Echo-MRI. At PN105, fasted (4 h) mice were sacrificed for serum and tissue analysis. Results: At PN42, mice in both galactose-fed groups (GLUGAL and GAL) had a significantly lower body weight, fat mass and relative fat mass compared with the MDX group (p < 0.0001). The respiratory exchange ratio was significantly lower in both galactose-fed groups compared with the MDX group (p < 0.05), suggesting lower carbohydrate oxidation and thus higher relative fat oxidation levels. In parallel, both galactose-fed groups showed lower energy expenditure (p < 0.05). Discussion: The GAL mice were similar to the GLUGAL (lactose mimic) mice in terms of body weight, composition and energy metabolism, while being significantly different from the MDX group at PN42. These findings suggest an improvement of body composition and energy metabolism when replacing MDX with galactose. This study is the first to compare the effects of replacing part of MDX with galactose in early life and reinforces the impact of the type of carbohydrates on metabolic outcomes.

Semi-synthetic and grain-based diets are common rodent diets for biomedical research. Both diet types are considered nutritionally adequate to support breeding, growth, and long life, yet there are fundamental differences between them that may affect metabolic processes. We have characterized the effects of diet type on breeding outcomes, metabolic phenotype, and microbiota profile in adult mice. Healthy 8-week-old female and male C57BL/6J mice were fed a semi-synthetic or a grain-based diet for 12 weeks and changes in body weight and body composition were monitored. Breeding outcomes were determined. Body fat accumulation of female mice was lower on the semi-synthetic diet than on the grain-based diet. Pregnancy rate and newborn pup survival appeared to be lower in mice exposed to semi-synthetic diet compared to grain-based diet. Both female and male mice showed a profound change in fecal microbiota alpha and beta diversity depending on diet type. Our study shows that type of rodent diet may affect breeding outcomes whilst influencing metabolism and health of female laboratory mice. These factors have the potential to influence other experimental outcomes and the results suggest that semi-synthetic and grain-based diets are not interchangeable in research using rodent models. Careful consideration and increased understanding of the consequences of diet choice would lead to improvements in experimental design and reproducibility of study results.

Background: Breastfeeding has been positively associated with infant and child neurocognitive development and function. Contributing to this effect may be differences between human milk and infant formula in the milk lipid composition and milk fat globule structure.Objective: To evaluate the effects of an infant formula mimicking human milk lipid composition and milk fat globule structure on childhood cognitive performance.Methods: In a randomized, controlled trial, healthy term infants received until 4 months of age either a Standard infant formula (n = 108) or a Concept infant formula (n = 115) with large, milk phospholipid coated lipid droplets and containing dairy lipids. A breastfed reference group (n = 88) was included. Erythrocyte fatty acid composition was determined at 3 months of age. Neurocognitive function was assessed as exploratory follow-up outcome at 3, 4, and 5 years of age using the Flanker test, Dimensional Change Card Sort (DCCS) test and Picture Sequence Memory test from the National Institutes of Health Toolbox Cognition Battery. Mann–Whitney U test and Fisher exact test were used to compare groups.Results: Erythrocyte omega-6 to -3 long-chain polyunsaturated fatty acid ratio appeared to be lower in the Concept compared to the Standard group (P = 0.025). At age 5, only the Concept group was comparable to the Breastfed group in the highest reached levels on the Flanker test, and the DCCS computed score was higher in the Concept compared to the Standard group (P = 0.021).Conclusion: These outcomes suggest that exposure to an infant formula mimicking human milk lipid composition and milk fat globule structure positively affects child neurocognitive development. Underlying mechanisms may include a different omega-3 fatty acid status during the first months of life.Clinical trial registration: https://onderzoekmetmensen.nl/en/trial/28614, identifier NTR3683 and NTR5538.

Breastfeeding (duration) can be positively associated with infant growth outcomes as well as improved cognitive functions during childhood and later life stages. (Prolonged) exposure to optimal lipid quantity and quality, i.e., the supramolecular structure of lipids, in mammalian milk, may contribute to these beneficial effects through nutritional early-life programming. In this pre-clinical study, we exposed male C57BL/6J mice from post-natal Days 16 to 42 (i.e., directly following normal lactation), to a diet with large lipid droplets coated with bovine milk fat globule membrane-derived phospholipids, which mimic more closely the supramolecular structure of lipid droplets in mammalian milk. We investigated whether exposure to this diet could affect growth and brain development-related parameters. As these outcomes are also known to be affected by the post-weaning social environment in mice, we included both individually housed and pair-wise housed animals and studied whether effects of diet were modulated by the social environment. After Day 42, all the animals were fed standard semi-synthetic rodent diet. Growth and body composition were assessed, and the mice were subjected to various behavioral tests. Individual housing attenuated adolescent growth, reduced femur length, and increased body fat mass. Adult social interest was increased due to individual housing, while cognitive and behavioral alterations as a result of different housing conditions were modest. The diet increased adolescent growth and femur length, increased lean body mass, reduced adolescent anxiety, and improved adult cognitive performance. These effects of diet exposure were comparable between individually and socially housed mice. Hence, early life exposure to a diet with lipid droplets that mimic the supramolecular structure of those in mammalian milk may improve adolescent growth and alters brain function in both socially and individually housed mice. These findings suggest that lipid structure in infant milk formula may be a relevant target for nutritional solutions, targeting both healthy infants and infants facing growth challenges.