Developmental trajectory of the healthy human gut microbiota during the first 5 years of life

The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota is still relatively unknown. Here, we analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory

Fetma och övervikt i barndomen - tidig identifiering av riskfaktorer

Background: The incidence of childhood obesity is increasing. Many children become obese during preschool years and stay obese, with lifelong health consequences, such as impaired insulin sensitivity. There is growing evidence that factors during intrauterine life and infancy influence the risk of developing obesity. The aim was to describe early factors in infancy related to childhood obesity. Research questions: Is waist circumference an auxological variable to be used in early childhood and is this variable related to early metabolic markers? Can biomarkers of bone and nutrition during infancy predict the development of childhood obesity and insulin resistance? How is the gut microbiota established during infancy and influenced by nutrition? Is any gut microbiota pattern during infancy associated with subsequent weight gain or the development of childhood obesity? Methodology: Paper 1: A cross-sectional population-based study comprising 4,500 children aged 0-5 years were followed at the child health clinic (CHC) in the County of Halland in 2006. Data on height, weight and waist circumference (WC) were collected from 6-60 months. Reference curves for WC were developed using the Box-Cox-power exponential (BCPE) distribution. Paper 2: Waist circumferences and BMI were investigated in moderately preterm preschool children (n=154), a group known to have increased risk of impaired insulin sensitivity. Paper 3 and 4: 388 healthy children were followed from birth to three years of age. Blood and stool samples were collected (cord, at 4, 12 and 36 months). Parents filled in questionnaires regarding hereditary, social factors and feeding preferences and anthropometric data was collected at the CHC. Fecal samples (n=100 at birth, 4 and 12 months) were analyzed with whole genome shotgun sequencing. Results: Swedish reference curves for WC and waist to height ratio for preschool children were constructed and found comparable to contemporary curves from Germany. Waist to height ratio declined from birth and reached a mean less than 0.5 first at five years of age. A cohort of moderately preterm children was compared to the new reference curves and were found to have an increased WC at 2 years of age despite being lean. In healthy children, multivariate regression analysis showed that neonatal levels of osteocalcin and vitamin D were predictors of body composition at three years of age. Early feeding patterns influenced levels of bone markers and BMI development. The early development of gut microbiota in 100 of the above mentioned children was described from birth to 12 months and compared with the gut microbiome of the mother. The gut microbiota evolved from low abundance to a more adult-like microbiota at one year of age and the early establishment was influenced by feeding patterns. Conclusion: We investigated the longitudinal development of obesity and found that early nutrition correlated to factors like gut microbiota, bone markers, insulin and leptin sensitivity as well as BMI and WC in early childhood

Salivary microflora and mode of delivery:a prospective case control study

BACKGROUND: Previous cross-sectional studies have suggested that the mode of delivery can influence the composition of oral microflora. The aim of this prospective study was to compare the salivary colonization in vaginally delivered children with children delivered by Caesarian section (C-section) during their first 6 months of life. METHODS: The study group consisted of 149 consecutively enrolled infants, delivered either vaginally (n = 96) or by C-section (n = 53) that volunteered after consent of their parents. Saliva samples were collected within 2 days after birth and then after 1, 3, and 6 months. A saliva sample from the mothers was obtained 6 months after delivery. The parents were asked to complete a questionnaire on socioeconomic factors, lifestyle, and hygiene at baseline and throughout the study period. All samples were analyzed with 13 pre-determined bacterial probes using checkerboard DNA-DNA hybridization. RESULTS: The groups were balanced at baseline concerning all relevant background factors. Gram-positive streptococci (S. mitis, S. salivarius) displayed the highest counts in both groups but a greater diversity was observed in the vaginally delivered group. A. naeslundi, A. odontolytics, F. nucleatum and L. salivarius were only detected among the vaginally delivered infants. The prevalence of S. sanguinis, S. gordoni, R. denticariosa, and B. dentinum increased by age in both groups but the prevalence was significantly lower in the C-section group (p < 0.05). There was a link between the mothers and their offspring’s concerning the salivary microbial profile. CONCLUSION: The microbial composition in saliva differs by the mode of delivery during the first six months of life

Serum osteocalcin levels at 4 months of age were associated with neurodevelopment at 4 years of age in term-born children

Aim: The hormone osteocalcin influenced neurodevelopment and cognition in mice models; this human study explored potential associations between total serum levels in human infants and neurodevelopment at 4 years of age. Methods: The data were based on two Swedish birth cohorts from 2008 to 2009. We followed 158 healthy full-term vaginal births (51% girls) by measuring serum osteocalcin in cord blood and at 4, 12 and 36 months. The values were compared with neurodevelopment tests at 4 years of age. Results: There was an association between osteocalcin at 4 months and later full-scale intelligence quotient (IQ; r(2) 0.031, p &lt; 0.05). Children with osteocalcin levels in the highest quartile scored 5.6 (95% confidence interval [1.3, 9.9]) points higher than those in the lowest quartile, with mean scores of 118.8 +/- 8.8 and 113.2 +/- 9.2 (p &lt; 0.05). They also scored higher on gross motor skills (p &lt; 0.05) and showed greater ability during the drawing trail test (p &lt; 0.005). Cord levels of osteocalcin were negatively associated with processing speed and fine motor development at 4 years, but levels at 12 and 36 months were not associated with later neurodevelopment. Conclusion: Osteocalcin levels in infancy appeared to be associated with later IQ and motor development, but more research is needed

MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume

Context: Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children. Methods: Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included. Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T-2(star)) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured. Results: The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p &lt; 0.01), except for VAT FF and weight, positively with sBAT T-2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p &lt; 0.01). Conclusions: Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT

Overweight at four years of age in a Swedish birth cohort: influence of neighbourhood-level purchasing power

Abstract Background A number of child/parental factors have been shown to be significant predictors of childhood overweight, although a better understanding of possible contextual influences of neighbourhood-level characteristics might provide new insights leading to tailored, targeted interventions. The aim of this study was to explore the impact of neighbourhood purchasing power and its relationship with other known risk factors related to childhood overweight in a prospective birth cohort. Methods A prospective, population-based, birth-cohort study was conducted in south-western Sweden, comprising 2,666 infants born in 2007–2008. Childhood overweight was assessed by body mass index (BMI) data from follow-up examinations at four years of age (n = 2,026) and overweight defined according to the International Obesity Task Force. Using logistic regression analysis, the influential child/parental predictors were identified from the candidate predictors, viz. child’s gender, as well as birth weight adjusted for gestational age and parental factors at recruitment, including maternal smoking status, maternal BMI (before pregnancy), paternal BMI and parental educational level. The children’s residential parishes at follow-up were stratified by parish-level household purchasing power (<10 %, 10–19.9 %, 20–29.9 % and ≥30 % of all resident families with low purchasing power) and the “contextual” influence was analysed. In each such neighbourhood stratum, the adjusted overweight ratio (AOR), i.e. the ratio between the observed number of overweight children and the expected number, taking account of the influential child/parental predictors, was estimated. Results The prevalence of overweight at four years of age was 11.9 %. In the economically strongest neighbourhoods (i.e. <10 % of resident families with low purchasing power), the AOR was 0.60 (95 % confidence interval (CI): 0.34–0.98). The corresponding empirically Bayes-adjusted AOR was 0.73 (95 % CI: 0.46–1.02; 97 % posterior probability of AOR <1). In the other neighbourhood strata, the statistical evidence of a deviant AOR was weaker. Conclusion The economically strongest neighbourhoods had a lower prevalence than expected of overweight at four years of age. This finding should prompt studies to acquire more knowledge of potentially modifiable factors that differ between neighbourhoods and are related to childhood overweight, providing a basis for tailored, targeted interventions

Early life factors and oral microbial signatures define the risk of caries in a Swedish cohort of preschool children

The oral cavity harbors complex communities comprising bacteria, archaea, fungi, protozoa, and viruses. The oral microbiota is establish at birth and develops further during childhood, with early life factors such as birth mode, feeding practices, and oral hygiene, reported to influence this development and the susceptibility to caries. We here analyzed the oral bacterial composition in saliva of 260 Swedish children at two, three and five years of age using 16S rRNA gene profiling to examine its relation to environmental factors and caries development at five years of age. We were able to assign the salivary bacterial community in each child at each time point to one of seven distinct clusters. We observed an individual dynamic in the development of the oral microbiota related to early life factors, such as being first born, born by C-section, maternal perinatal antibiotics use, with a distinct transition between three and five years of age. Different bacterial signatures depending on age were related to increased caries risk, while Peptococcus consistently linked to reduced risk of caries development