Summary: The colonization of the gut with microbes in early life is critical to the developing newborn immune system, metabolic function and potentially future health. Maternal microbes are transmitted to offspring during childbirth, representing a key step in the colonization of the infant gut. Studies of infant meconium suggest that bacteria are present in the foetal gut prior to birth, meaning that colonization could occur prenatally. Animal studies have shown that prenatal transmission of microbes to the foetus is possible, and physiological changes observed in pregnant mothers indicate that in utero transfer is likely in humans as well. However, direct evidence of in utero transfer of bacteria in humans is lacking. Understanding the timing and mechanisms involved in the first colonization of the human gut is critical to a comprehensive understanding of the early life gut microbiome. This review will discuss the evidence supporting in utero transmission of microbes from mother to infants. We also review sources of transferred bacteria, physiological mechanisms of transfer and modifiers of maternal microbiomes and their potential role in early life infant health. Well‐designed longitudinal birth studies that account for established modifiers of the gut microbiome are challenging, but will be necessary to confirm in utero transfer and further our knowledge of the prenatal microbiome.

Melanocortin 4 receptor (MC4R) deficiency, caused by mutations in MC4R, is the most common cause of monogenic forms of obesity. However, these mutations have often been identified in small-scale, case-focused studies. Here, we assess the penetrance of previously reported MC4R mutations at a population level. Furthermore, we examine why some carriers of pathogenic mutations remain of normal weight, to gain insight into the mechanisms that control body weight. We identified 59 known obesity-increasing mutations in MC4R from the Human Gene Mutation Database (HGMD) and Clinvar. We assessed their penetrance and effect on obesity (body mass index [BMI] ≥ 30 kg/m²) in >450,000 individuals (age 40–69 years) of the UK Biobank, a population-based cohort study. Of these 59 mutations, only 11 had moderate-to-high penetrance and increased the odds of obesity by more than 2-fold. We subsequently focused on these 11 mutations and examined differences between carriers of normal weight and carriers with obesity. Twenty-eight of the 182 carriers of these 11 mutations were of normal weight. Body composition of carriers of normal weight was similar to noncarriers of normal weight, whereas among individuals with obesity, carriers had a somewhat higher BMI than noncarriers (1.44 ± 0.07 standard deviation scores [SDSs] ± standard error [SE] versus 1.29 ± 0.001, P = 0.03), because of greater lean mass (1.44 ± 0.09 versus 1.15 ± 0.002, P = 0.002). Carriers of normal weight more often reported that, already at age 10 years, their body size was below average or average (72%) compared with carriers with obesity (48%) (P = 0.01). To assess the polygenic contribution to body weight in carriers of normal weight and carriers with obesity, we calculated a genome-wide polygenic risk score for BMI (PRS_BMI). The PRS_BMI of carriers of normal weight (PRS_BMI = -0.64 ± 0.18) was significantly lower than of carriers with obesity (0.40 ± 0.11; P = 1.7 × 10⁻⁶), and tended to be lower than that of noncarriers of normal weight (−0.29 ± 0.003; P = 0.05). Among carriers, those with a low PRS_BMI (bottom quartile) have an approximately 5-kg/m² lower BMI (approximately 14 kg of body weight for a 1.7-m-tall person) than those with a high PRS (top quartile). Because the UK Biobank population is healthier than the general population in the United Kingdom, penetrance may have been somewhat underestimated. We showed that large-scale data are needed to validate the impact of mutations observed in small-scale and case-focused studies. Furthermore, we observed that despite the key role of MC4R in obesity, the effects of pathogenic MC4R mutations may be countered, at least in part, by a low polygenic risk potentially representing other innate mechanisms implicated in body weight regulation.

Excess added sugar consumption is tied to poor health outcomes in children. The sugar content of beverages and foods children are exposed to is mostly unknown, yet this information is imperative for understanding potential risks from overconsumption of sugars in early life. We determined actual sugar content by conducting a blinded laboratory analysis in infant formulas, breakfast cereals, packaged baked goods and yogurts. One hundred samples were sent to an independent laboratory for analysis via gas chromatography. Sugar content and composition was determined and total sugar was compared against nutrition labels. Of the 100 samples analyzed, 74% contained ≥20% of total calories per serving from added sugars. Nutrient label data underestimated or overestimated actual sugars and ~25% of all samples had actual total sugar values that were either 10% of labeled total sugar. Many products that are frequently marketed to and consumed by infants and young children contain sugars in amounts that differ from nutrition labels and often in excess of recommended daily levels. These findings provide further support for adding more comprehensive sugar labeling to food and beverage products, specifically those marketed to, or commonly consumed by, children.

Objective Obesity in childhood is associated with an inflammatory state in adipose tissue and liver, which elevates risk for diabetes and liver disease. No prior study has examined associations between pathologies occurring in adipose tissue and liver to identify elements of tissue damage associated with type 2 diabetes risk. This study sought to determine whether inflammation and fibrosis in abdominal subcutaneous adipose tissue (SAT) in obese/overweight children (BMI‐z 2.3 ± 0.76) was related to the extent of observed liver disease or type 2 diabetes risk. Methods Biopsy samples of abdominal (SAT) and liver were simultaneously collected from 33 Italian children (mean BMI 28.1 ± 5.1 kg/m² and mean age 11.6 ± 2.2 years) with confirmed NAFLD. Histology and immunohistochemistry were conducted on biopsies to assess inflammation and fibrosis in adipose tissue and fibrosis and inflammation in liver. Results Presence vs. absence of crown‐like structures (CLS) in SAT was significantly related to liver fibrosis scores (1.7 ± 0.7 vs. 1.2 ± 0.7, P = 0.04) independent of BMI. SAT fibrosis was significantly correlated with a lower disposition index (r = −0.48, P = 0.006). No other adipose measures were associated with liver disease parameters. Conclusion Markers of subcutaneous white adipose tissue inflammation are associated with greater extent of liver fibrosis independent of obesity and SAT fibrosis may contribute to diabetes risk through reduced insulin secretion.

Background: The association between high fructose consumption and elevated blood pressure continues to be controversial, especially in adolescence. The aim of this study was to assess the association between fructose consumption and elevated blood pressure in an European adolescent population. Methods: A total of 1733 adolescents (mean ± SD age: 14.7 ± 1.2; percentage of girls: 52.8%) were analysed from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study in eight European countries. Blood pressure was measured using validated devices and methods for measuring systolic blood pressure (SBP) and diastolic blood pressure (DBP). Dietary data were recorded via repeated 24 h recalls (using specifically developed HELENA–DIAT software) and converted into pure fructose (monosaccharide form) and total fructose exposure (pure fructose + fructose from sucrose) intake using a specific fructose composition database. Food categories were separated at posteriori in natural vs. were non-natural foods. Elevated BP was defined according to the 90th percentile cut-off values and was compared according to tertiles of fructose intake using univariable and multivariable mixed logistic regression models taking into account confounding factors: centre, sex, age and z-score–BMI, MVPA (Moderate to Vigorous Physical Activity) duration, tobacco consumption, salt intake and energy intake. Results: Pure fructose from non-natural foods was only associated with elevated DBP (DBP above the 10th percentile in the highest consuming girls (OR = 2.27 (1.17–4.40); p = 0.015) after adjustment for cofounding factors. Conclusions: Consuming high quantities of non-natural foods was associated with elevated DBP in adolescent girls, which was in part due to high fructose levels in these foods categories. The consumption of natural foods containing fructose, such as whole fruits, does not impact blood pressure and should continue to remain a healthy dietary habit.