Liene Bervoets

Differences in gut microbiota composition between obese and lean children: a cross-sectional study.

BackgroundAn altered gut microbiota composition has recently been linked to obesity. The principal aim of this study is to investigate and compare the gut microbiota composition in obese and lean children. Secondly, associations between analysed gut bacterial species, dietary compounds, energy intake and biochemical blood parameters are evaluated.MethodsIn this prospective cross-sectional study, 26 overweight/obese (mean BMI: 28.7 ± 6.5) and 27 lean (mean BMI: 16.5 ± 2.1) children aged 6 to 16 were included. Faecal samples were collected and subjected to selective plating and quantitative real-time PCR (qPCR) in order to determine the concentrations of bacterial species belonging to the genera: Bacteroides, Bifidobacterium, Clostridium, Staphylococcus and Lactobacillus. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for an in-depth identification of species of Bacteroides fragilis group. Differences in the concentrations of gut bacterial species between obese and lean children were statistically analysed using Mann Whitney U test. Subsequently, random forest analysis and multiple linear regression analysis were performed in order to test associations between gut bacterial species, dietary compounds and blood parameters.ResultsObese children showed an elevated Firmicutes-to-Bacteroidetes ratio compared with lean children. Furthermore, low relative proportions of B. vulgatus and high concentrations of Lactobacillus spp. were observed in the obese microbiota. In all children, Staphylococcus spp. were positively associated with energy intake. Additionally, in obese children, Lactobacillus spp. were positively associated with plasma hs-CRP.ConclusionsOur findings corroborate a significant difference in the gut microbiota composition of important bacterial species between obese and lean children. In future, non-invasive manipulation of gut microbiota composition in early infancy could offer a new approach to manage childhood obesity and associated disorders.

Defining morbid obesity in children based on BMI 40 at age 18 using the extended international (IOTF) cut‐offs

Studies have reported that children who are obese are becoming more severely obese.

Reliability and Validity of the Dutch Physical Activity Questionnaires for Children (PAQ-C) and Adolescents (PAQ-A).

BackgroundThis study was designed to validate the Dutch Physical Activity Questionnaires for Children (PAQ-C) and Adolescents (PAQ-A).MethodsAfter adjustment of the original Canadian PAQ-C and PAQ-A (i.e. translation/back-translation and evaluation by expert committee), content validity of both PAQs was assessed and calculated using item-level (I-CVI) and scale-level (S-CVI) content validity indexes. Inter-item and inter-rater reliability of 196 PAQ-C and 95 PAQ-A filled in by both children or adolescents and their parent, were evaluated. Inter-item reliability was calculated by Cronbach’s alpha (α) and inter-rater reliability was examined by percent observed agreement and weighted kappa (κ). Concurrent validity of PAQ-A was examined in a subsample of 28 obese and 16 normal-weight children by comparing it with concurrently measured physical activity using a maximal cardiopulmonary exercise test for the assessment of peak oxygen uptake (VO2 peak).ResultsFor both PAQs, I-CVI ranged 0.67-1.00. S-CVI was 0.89 for PAQ-C and 0.90 for PAQ-A. A total of 192 PAQ-C and 94 PAQ-A were fully completed by both child and parent. Cronbach’s α was 0.777 for PAQ-C and 0.758 for PAQ-A. Percent agreement ranged 59.9-74.0% for PAQ-C and 51.1-77.7% for PAQ-A, and weighted κ ranged 0.48-0.69 for PAQ-C and 0.51-0.68 for PAQ-A. The correlation between total PAQ-A score and VO2 peak – corrected for age, gender, height and weight – was 0.516 (p = 0.001).ConclusionsBoth PAQs have an excellent content validity, an acceptable inter-item reliability and a moderate to good strength of inter-rater agreement. In addition, total PAQ-A score showed a moderate positive correlation with VO2 peak. Both PAQs have an acceptable to good reliability and validity, however, further validity testing is recommended to provide a more complete assessment of both PAQs.

Classification and clinical characterization of metabolically “healthy” obese children and adolescents

Abstract Background: Some obese children do not show cardiometabolic complications such as prediabetes, dyslipidemia or insulin resistance. The objective of the study was to classify obese children and adolescents as metabolically “healthy” obese (MHO) on the basis of three different definitions, and to compare cardiometabolic features with metabolically unhealthy obese (MUO) children and adolescents. Methods: The study included 156 obese children and adolescents aged between 10 and 18. Subjects were classified as MHO or MUO using three definitions based on the: (1) pediatric International Diabetes Federation (IDF) criteria; (2) homeostatic model assessment of insulin resistance (HOMA-IR); (3) combination of the previous two definitions. Cardiometabolic features were compared between MHO and MUO subjects. Results: Six to 19% obese children and adolescents were classified as MHO, and showed a better insulin sensitivity, lower prevalence of prediabetes, lower triglycerides and lower triglyceride-to-HDL-C ratio compared to MUO. Conclusions: Less than 20% obese children and adolescents are identified as MHO and show a healthier cardiometabolic profile as compared to MUO. Implementation of the proposed classifications in future clinical research could contribute towards the standardization of the MHO definition and offer new insights into the manifestation of the pediatric MHO phenotype.

The shape of the plasma glucose curve during an oral glucose tolerance test as an indicator of Beta cell function and insulin sensitivity in end-pubertal obese girls.

It is hypothesized that the shape of the glucose curve during an oral glucose tolerance test is an early indicator of the risk for developing type 2 diabetes mellitus. In this study, we aimed to examine the shape of plasma glucose response curves and study their relationship with insulin sensitivity, insulin secretion and components of the metabolic syndrome in end-pubertal obese girls. Eighty-one end-pubertal obese girls [median (range) age: 14.4 (11.2-18.0) years; BMI: 34.6 (25.4-50.8) kg/m(²)] who underwent a 2-h oral glucose tolerance test were classified according to the shape of the glucose curve. Four shape types of the plasma glucose response curve were observed: 28 (34.6%) monophasic, 30 (37.0%) biphasic, 14 (17.3%) triphasic, and 9 (11.1%) unclassified. Patients with a monophasic shape had a higher area under the curve for glucose (p = 0.008), a lower early-phase insulin secretion (p = 0.005), and a poorer beta cell function relative to insulin sensitivity as reflected by the oral disposition index (p = 0.022) compared to the bi- and triphasic shape types. In addition, the triglyceride level and TG/HDL-C ratio was higher in patients with a monophasic shape compared to those with a biphasic shape (p = 0.040 and p = 0.048, respectively). In conclusion, end-pubertal obese girls with a monophasic plasma glucose curve are at increased risk for insulin resistance, which can contribute to the development of type 2 diabetes mellitus and cardiovascular diseases.

Metabolic phenotyping of human plasma by 1H-NMR at high and medium magnetic field strengths: a case study for lung cancer: High-field (900 MHz) versus medium-field (400 MHz) NMR metabolomics

Accurate identification and quantification of human plasma metabolites can be challenging in crowded regions of the NMR spectrum with severe signal overlap. Therefore, this study describes metabolite spiking experiments on the basis of which the NMR spectrum can be rationally segmented into well‐defined integration regions, and this for spectrometers having magnetic field strengths corresponding to 1H resonance frequencies of 400 MHz and 900 MHz. Subsequently, the integration data of a case–control dataset of 69 lung cancer patients and 74 controls were used to train a multivariate statistical classification model for both field strengths. In this way, the advantages/disadvantages of high versus medium magnetic field strength were evaluated. The discriminative power obtained from the data collected at the two magnetic field strengths is rather similar, i.e. a sensitivity and specificity of respectively 90 and 97% for the 400 MHz data versus 88 and 96% for the 900 MHz data. This shows that a medium‐field NMR spectrometer (400–600 MHz) is already sufficient to perform clinical metabolomics. However, the improved spectral resolution (reduced signal overlap) and signal‐to‐noise ratio of 900 MHz spectra yield more integration regions that represent a single metabolite. This will simplify the unraveling and understanding of the related, disease disturbed, biochemical pathways. Copyright

Identification of metabolic phenotypes in childhood obesity by 1H NMR metabolomics of blood plasma

Aim: To identify the plasma metabolic profile associated with childhood obesity and its metabolic phenotypes. Materials & methods: The plasma metabolic profile of 65 obese and 37 normal-weight children was obtained using proton NMR spectroscopy. NMR spectra were rationally divided into 110 integration regions, which reflect relative metabolite concentrations, and were used as statistical variables. Results: Obese children show increased levels of lipids, N-acetyl glycoproteins, and lactate, and decreased levels of several amino acids, α-ketoglutarate, glucose, citrate, and cholinated phospholipids as compared with normal-weight children. Metabolically healthy children show lower levels of lipids and lactate, and higher levels of several amino acids and cholinated phospholipids, as compared with unhealthy children. Conclusion: This study reveals new valuable findings in the field of metabolomics and childhood obesity. Although validation should be performed, the proof of principle looks promising and justifies a deeper investigation of the diagnostic possibilities of proton NMR metabolomics in follow-up studies. Trial registration: NCT03014856. Registered January 9, 2017.