Background: Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components. Methods: This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components. Results: The study was conducted with 174 children/adolescents aged 6-17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-bodyweight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score.

Differentiation of the digestive tube and formation of the gut unit as a whole, are regulated by environmental factors through epigenetic modifications which enhance cellular plasticity. The critical period of DNA imprinting lasts from conception until approximately the 1,000th day of human life. During pregnancy, besides agents that may directly promote epigenetic programming (e.g., folate, zinc, and choline supplementation), some factors (e.g., antibiotic use, dietary components) can affect the composition of the mother's microbiota, in turn affecting the fetal microbiome which interacts with the offspring's intestinal epithelial cells. According to available literature that confirms intrauterine microbial colonization, the impact of the microbiome and its metabolites on the genome seems to be key in fetal development, including functional gut maturation and the general health status of the offspring, as well as later on in life. Although the origin of the fetal microbiome is still not well-understood, the bacteria may originate from both the vagina, as the baby is born, as well as from the maternal oral cavity/gut, through the bloodstream. Moreover, the composition of the fetal gut microbiota varies depending on gestational age, which in turn possibly affects the regulation of the immune system at the barrier between mother and fetus, leading to differences in the ability of microorganisms to access and survive in the fetal environment. One of the most important local functions of the gut microbiota during the prenatal period is their exposure to foreign antigens which in turn contributes to immune system and tissue development, including fetal intestinal Innate Lymphoid Cells (ILCs). Additional factors that determine further infant microbiome development include whether the infant is born premature or at term, the method of delivery, maternal antibiotic use, and the composition of the mother's milk, among others. However, the latest findings highlight the fact that a more diverse infant gut microbiome at birth facilitates the proliferation of stem cells by microbial metabolites and accelerates infant development. This phenomenon confirms the unique role of microbiome. This review emphasizes the crucial perinatal and postnatal factors that may influence fetal and neonatal microbiota, and in turn gut maturation.

IntroductionThe results of some previous studies suggested that maternal folate supplementation during pregnancy may contribute to allergy development in offspring.AimThis study was performed to examine the influence of maternal folic acid intake prior to and during pregnancy on the development of various types of allergy in children taking into account the timing and dosage of supplemented folate.Material and methodsThe retrospective study was performed between 2010 and 2014 in 307 child-mother pairs (203 allergic children and 104 children without allergy symptoms, aged 2–72 months). Allergy diagnosis was based on medical history, physical examination, positive results of allergic tests: specific IgE and/or skin prick tests and double-blind, placebo-controlled food challenge. The data concerning maternal folate supplementation prior to and during pregnancy were obtained based on a questionnaire.ResultsMothers of allergic children used to take folic acid more frequently in the preconception period (42.9%), in the 1st (94.1%) and the 2nd/3rd (81.3%) trimester of pregnancy than mothers of the healthy ones (30.8%, 82.7% and 55.8%, respectively) (p < 0.05). Maternal intake of folate in a dosage higher than recommended (> 0.4 mg/day) was more often observed in the group of allergic subjects, especially in children with combined sensitization to food and inhalant allergens, than in the control group (p < 0.05).ConclusionsOur results suggest an impact of maternal folic acid supplementation prior to and during pregnancy on allergy development in children. Further observations are required to establish the role of folate in fetal epigenetic modifications.

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The study comprised 318 children in their first four years of life, treated for various medical conditions. The examined children were divided into two groups, Group 1--children exposed to Tobacco smoke--and Group 2--a control group with children from non-smoking families. History data were obtained on the basis of a specially designed questionnaire, used by the doctor in an individual conversation with parent. In each third child from the group 1 cotinine concentration in urine was assayed by the method of high performance liquid chromatography-UV-VIS and the cotinine/creatinine ratio was calculated. RESULTS OF STUDY: Results demonstrated environmental exposure to tobacco smoke in 173 children (Group 1). Out of them 31.2% were the children whose mothers had smoked also during pregnancy (Subgroup A). The other 119 children from Group 1 were accounted to Subgroup B, i.e., children, where other household members had been smoking cigarettes. A comparative group comprised 143 children from non-smoking families. The results demonstrated then that 17% of all the examined children were those, exposed to tobacco smoke effects already in their foetal life, predisposing them to prematurity and low birth weight. Moreover, it was observed that the young age and lower education level of their parents, together with worse housing conditions, may suggest a predisposing character and role of the mentioned factors.

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Pancreatic enzyme replacement therapy (PERT) and fat predigestion are key in ensuring the optimal growth of patients with cystic fibrosis. Our study attempted to highlight differences between fat predigestion and conventional PERT on body composition of young pigs with exocrine pancreatic insufficiency (EPI). EPI and healthy pigs were fed with high-fat diet for six weeks. During the last two weeks of the study, all pigs received additional nocturnal alimentation with Peptamen AF (PAF) and were divided into three groups: H—healthy pigs receiving PAF; P—EPI pigs receiving PAF+PERT; and L—EPI pigs receiving PAF predigested with an immobilized microbial lipase. Additional nocturnal alimentation increased the body weight gain of EPI pigs with better efficacy in P pigs. Humerus length and area in pigs in groups L and P were lower than that observed in pigs in group H ( p value 0.005-0.088). However, bone mineral density and strength were significantly higher in P and L as compared to that of H pigs ( p value 0.0026-0.0739). The gut structure was improved in P pigs. The levels of neurospecific proteins measured in the brain were mainly affected in P and less in L pigs as compared to H pigs. The beneficial effects of the nocturnal feeding with the semielemental diet in the prevention of EPI pigs’ growth/development retardation are differently modified by PERT or fat predigestion in terms of growth, bone properties, neurospecific protein distribution, and gut structure.

In recent years, there has been a noticeable increase in the incidence of inflammatory bowel diseases in the pediatric population. Entry observations demonstrate anemia, malabsorption, deficiencies in vitamin D and calcium. These aspects, together with the systemic action of pro-inflammatory cytokines and steroid therapy are widely recognized as factors influencing bone metabolism. Presently, however, there are very few studies that can be found in the scientific literature on metabolic disorders in patients with IBD, especially in the pediatric population as the coexistence has not been sufficiently examined and understood. This review aims to summarize the currently available literature, as well as assess which areas have information gaps and need further research.