Serum, Urine, and Fecal Metabolome Alterations in the Gut Microbiota in Response to Lifestyle Interventions in Pediatric Obesity: A Non-Randomized Clinical Trial.

Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + ß acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.

Noninvasive assessment of paediatric hepatic steatosis by using attenuation imaging.

OBJECTIVES: To evaluate the diagnostic performance of attenuation imaging (ATI) with an ultrasound scanner (US) in the detection of paediatric hepatic steatosis. METHODS: Ninety-four prospectively enrolled children were classified into normal weight and overweight/obese (OW/OB) groups according to body mass index (BMI). US findings, including hepatic steatosis grade and ATI value, were examined by two radiologists. Anthropometric and biochemical parameters were obtained, and nonalcoholic fatty liver disease (NAFLD) scores, including the Framingham steatosis index (FSI) and hepatic steatosis index (HSI), were calculated. RESULTS: After screening, 49 OW/OB and 40 normal weight children aged 10-18 years old (55 males and 34 females) participated in this study. The ATI value was significantly higher in the OW/OB group than in the normal weight group and showed a significant positive correlation with BMI, serum alanine transferase (ALT), uric acid, and NAFLD scores (p < 0.05). In the multiple linear regression adjusted for age, sex, BMI, ALT, uric acid, and HSI, ATI showed a significant positive association with BMI and ALT (p < 0.05). The receiver operating characteristic analysis showed a very good ability of ATI to predict hepatic steatosis. The intraclass correlation coefficient (ICC) of interobserver variability was 0.92, and the ICCs of intraobserver variability were 0.96 and 0.93 (p < 0.05). According to the two-level Bayesian latent class model analysis, the diagnostic performance of ATI showed the best performance for predicting hepatic steatosis among other known noninvasive NAFLD predictors. CONCLUSIONS: This study suggests that ATI is an objective and possible surrogate screening test for detecting hepatic steatosis in paediatric patients with obesity. CLINICAL RELEVANCE STATEMENT: Using ATI as a quantitative tool in hepatic steatosis allows clinicians to estimate the extent of the condition and track changes over time. This is helpful for monitoring disease progression and guiding treatment decisions, especially in paediatric practice. KEY POINTS: • Attenuation imaging is a noninvasive US-based method for the quantification of hepatic steatosis. • Attenuation imaging values were significantly higher in the OW/OB and steatosis groups than in the normal weight and no steatosis groups, respectively, with a meaningful correlation with known clinical indicators of nonalcoholic fatty liver disease. • Attenuation imaging performs better than other noninvasive predictive models used to diagnose hepatic steatosis.

Association of gut microbiota with obesity in children and adolescents.

Pediatric obesity is among the most serious global health problems whose prevalence has increased over the past decade. Pediatric obesity increases concomitant health problems, including type 2 diabetes mellitus, hypertension, dyslipidemia, fatty liver disease, and psychological problems, which often progress into adulthood. The gut microbiota is a new factor in the development of obesity, which is affected by renowned risk factors such as diet, lifestyle, and socioeconomic status. This review aimed to describe the association between the gut microbiota and childhood obesity. According to advances in gene sequencing technologies, many findings of experimental animal and human studies of adults and children demonstrated that compositional and functional changes in the gut microbiota (dysbiosis) are associated with the development of obesity. Many studies have reported that an increased Firmicutes/Bacteroidetes (F/B) ratio is a biomarker of obesity susceptibility; however, with the rapid accumulation of data, meta-analyses of human gut microbiota and obesity showed no clear association between F/B ratio and obesity status. The contribution of the microbiota to obesity has been considered using multifactorial approaches, such as supplying additional calories to the host, modulating blood lipopolysaccharide levels, favoring fat storage, and affecting satiety. Probiotics are proposed to manipulate the gut microbiota population to improve obesity; however, their clinical application remains limited because trials have shown different results. Further studies are required to better understand the mechanisms underlying the observed association between the gut microbiota and pediatric obesity.

Association of Blood Mercury Levels with the Risks of Overweight and High Waist-to-Height Ratio in Children and Adolescents: Data from the Korean National Health and Nutrition Examination Survey.

A previous study in adults demonstrated the substantial role of mercury exposure in the development of overweight and obesity. Although children and adolescents are more susceptible to the toxic effects of mercury than adults, studies on the association of overweight and obesity with mercury exposure is limited. This study aimed to investigate the association of blood mercury levels with the body mass index (BMI) and waist-to-height ratio (WHtR) as obesity indices in Korean children and adolescents. The analyzed cross-sectional data were obtained from 1327 participants (age: 10-18 years; 672 male and 655 female) who completed the Korean National Health and Nutrition Examination Survey 2010-2013. The covariates included sociodemographic factors (age, sex, and household income), dietary factors (fish, shellfish, and seaweed consumption), lifestyle factors (alcohol consumption, smoking status, and exercise), and blood hematocrit levels. The adjusted geometric mean blood mercury level was 2.19 µg/L, and the level of mercury was significantly higher in the overweight (BMI ≥ 85th gender and age-specific percentiles) and high WHtR (cutoff: ≥0.5) groups than in the normal group. In all the participants, the blood mercury levels were significantly positively associated with the BMI and WHtR after adjusting for all covariates (p < 0.05). All the participants in the highest blood mercury level quartile were at a higher risk for overweight and a high WHtR than those in the lowest quartile after adjusting for all covariates (p < 0.05). Our study suggests a significant association between mercury exposure and the risks of overweight and high WHtR in Korean children and adolescents.

Bowel Wall Thickening on Computed Tomography in Children: A Novel Method of Measurement and Its Clinical Significance.

PURPOSE: The clinical implications of bowel wall thickening (BWT) on abdominal computed tomography (CT) among children are unknown. We aimed to suggest a new method for measuring BWT and determining its clinical significance in children. METHODS: We retrospectively analyzed 423 patients with acute abdomen who underwent abdominal CT; 262 were classified into the BWT group. For this group, the pediatric radiologist described the maximal bowel wall thickness (MT), normal bowel wall thickness (mm) (NT), and their ratios for each segment of the bowel wall. RESULTS: In the thickened bowel walls, the thickness differed significantly between the small bowel (6.83±2.14 mm; mean±standard deviation) and the colon (8.56±3.46 mm; p<0.001). The ratios of MT to NT in the small bowel (6.09±3.17) and the colon (7.58±3.70) were also significantly different (p<0.001). In the BWT group, 35 of 53 patients had positive fecal polymerase chain reaction results; 6 patients infected with viruses predominantly had BWT in the small intestine, while the terminal ileum and the colon were predominantly affected in 29 patients with bacterial infections. In the initially undiagnosed 158 patients with BWT, the symptoms improved spontaneously without progression to chronic gastrointestinal disease. CONCLUSION: This study provides a clinical reference value for BWT in the small intestine and colon using a new method in children. The BWT on abdominal CT in children might indicate nonspecific findings that can be observed and followed up without additional evaluation, unlike in adults.

The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis.

An excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1ß-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA's effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.

Lifestyle modifications result in alterations in the gut microbiota in obese children.

BACKGROUND: The association between the gut microbiota and pediatric obesity was analyzed in a cross-sectional study. A prospective study of obese children was conducted to assess the gut microbial alterations after a weight change. We collected fecal samples from obese children before and after a 2-month weight reduction program that consisted of individual counseling for nutritional education and physical activity, and we performed 16S rRNA gene amplicon sequencing using an Illumina MiSeq platform. RESULTS: Thirty-six participants, aged 7 to 18 years, were classified into the fat loss (n = 17) and the fat gain (n = 19) groups according to the change in total body fat (%) after the intervention. The baseline analysis of the gut microbiota in the preintervention stages showed dysbiotic features of both groups compared with those of normal-weight children. In the fat loss group, significantly decreased proportions of Bacteroidetes phylum, Bacteroidia class, Bacteroidales order, Bacteroidaceae family, and Bacteroides genus, along with increased proportions of Firmicutes phylum, Clostridia class, and Clostridiales order, were observed after intervention. The microbial richness was significantly reduced, without a change in beta diversity in the fat loss group. The fat gain group showed significantly deceased proportions of Firmicutes phylum, Clostridia class, Clostridiales order, Lachnospiraceae family, and Eubacterium hallii group genus, without a change in diversity after the intervention. According to the functional metabolic analysis by the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2, the "Nitrate Reduction VI" and "Aspartate Superpathway" pathways were predicted to increase significantly in the fat loss group. The cooccurring networks of genera were constructed and showed the different microbes that drove the changes between the pre- and postintervention stages in the fat loss and fat gain groups. CONCLUSIONS: This study demonstrated that lifestyle modifications can impact the composition, richness, and predicted functional profiles of the gut microbiota in obese children after weight changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03812497 , registration date January 23, 2019, retrospectively registered.

Altered Gut Microbiota and Shift in Bacteroidetes between Young Obese and Normal-Weight Korean Children: A Cross-Sectional Observational Study.

Emerging data suggest that the gut microbiome is related to the pathophysiology of obesity. This study is aimed at characterizing the gut microbiota composition between obese and normal-weight Korean children aged 5-13. We collected fecal samples from 22 obese and 24 normal-weight children and performed 16S rRNA gene sequencing using the Illumina MiSeq platform. The relative abundance of the phylum Bacteroidetes was lower in the obese group than in the normal-weight group and showed a significant negative correlation with BMI z-score. Linear discriminative analysis (LDA) coupled with effect size measurement (LEfSe) analysis also revealed that the Bacteroidetes population drove the divergence between the groups. There was no difference in alpha diversity, but beta diversity was significantly different between the normal-weight and obese groups. The gut microbial community was linked to BMI z-score; blood biomarkers associated with inflammation and metabolic syndrome; and dietary intakes of niacin, sodium, vitamin B6, and fat. The gut microbiota of the obese group showed more clustering of genera than that of the normal-weight group. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis revealed that the functions related to carbohydrate and lipid metabolism in the microbiota were more enriched in the normal-weight group than in the obese group. Our data may contribute to the understanding of the gut microbial structure of young Korean children in relation to obesity. These findings suggest that Bacteroidetes may be a potential therapeutic target in pediatric obesity.

Risk Factors for Functional Constipation in Young Children Attending Daycare Centers.

Our objective was to determine the risk factors associated with the development of functional constipation (FC) in young children attending daycare centers. A cross-sectional survey using a questionnaire based on the Rome III criteria was conducted in children aged 25 to 84 months from 3 randomly selected daycare centers in January 2016. The items in a questionnaire were statistically compared in the constipated and non-constipated groups. A total of 212 children were included and FC was found in 8.5%. Multivariate logistic regression analyses revealed that maternal history of constipation (odds ratio [OR] = 4.1, 95% Confidence Interval [CI] 1.2-13.9), history of painful defecation before age 1 (OR = 10.4, 95% CI 1.1-101.3), history of painful defecation during toilet training (OR = 28.9, 95% CI 1.9-423.8), no or difficult defecation at a daycare center (OR = 5,804.6, 95% CI 134.4-250,718.4), no meat consumption (OR = 10.1, 95% CI 1.2-88.1), and 500 mL or less of water intake per day (OR = 9.9, 95% CI 0.9-99.5) were powerful predictors of FC in young children (P < 0.05). Additionally, the constipated group was significantly associated with 2 hours or less of outdoor play activities per day, entry into daycare centers before 24 months age, 6 hours or more of attendance at a daycare center per day, breastfeeding for less than 6 months, 3 meals or less per day, and 3 or fewer servings of fruits and vegetables per day (P < 0.05). The findings of this study can guide parents, daycare teachers, and clinicians in prevention, early recognition and early intervention for the risk factors associated with FC in young children.

Diagnostic value of the Vesikari Scoring System for predicting the viral or bacterial pathogens in pediatric gastroenteritis.

PURPOSE: To evaluate the diagnostic value of the Vesikari Scoring System (VSS) as an early predictor of pathogens in children with acute gastroenteritis (AG). METHODS: In this retrospective study, the VSS score, absolute neutrophil count (ANC), and C-reactive protein (CRP) levels were analyzed in 107 hospitalized children with AG, aged 6 months to 17 years. Patients were divided into nonspecific, viral, and bacterial groups according to the pathogens detected using a multiplex polymerase chain reaction (PCR) test. RESULTS: Patients in the bacterial group had significantly higher CRP values and VSS scores compared to those in the viral group and significantly higher VSS scores compared to those in the nonspecific group (P<0.05). Patients in the viral group had significantly higher VSS scores than those in the nonspecific group (P<0.05). Logistic regression analysis revealed that VSS was the most effective diagnostic tool for predicting the type of pathogen (P<0.05). The area under the receiver operating characteristics curve of VSS was significantly greater than that for ANC and CRP (P<0.05). At a cutoff point of 10 in the VSS, an acceptable diagnostic accuracy could be achieved for distinguishing between bacterial and viral pathogens in AG. CONCLUSION: VSS can be considered a useful and reliable infectious marker for pediatric gastroenteritis. VSS may be a good early predictor of the type of pathogen, enabling development of a treatment plan before results from a stool culture or PCR test are available.

Use of the Pediatric Appendicitis Score in a Community Hospital.

OBJECTIVE: To suggest the use of the Pediatric appendicitis score (PAS) for diagnosing acute pediatric appendicitis in a community hospital. METHODS: We retrospectively reviewed the data of 285 patients aged 3 to 17 years who underwent abdominal computed tomography (CT) for suspected acute appendicitis at a single community hospital. The PAS score was compared with the CT findings in the appendicitis (n=86) and non-appendicitis (n=199) group. RESULTS: The appendicitis group had a significantly higher PAS and more frequently positive CT findings for appendicitis than the non-appendicitis group (P<0.01). There were no significant differences in the diagnostic performance of the PAS and CT. Patients with a PAS of 1 to 3 could be discharged without further imaging study, those with a PAS of 4 to 6 might need to undergo further imaging study, and those with 7 to 10 PAS required surgical consultation with imaging study. CONCLUSIONS: The application of this score could help in reducing the reliance on CT and in standardizing the clinical assessment in a community hospital.

Small bowel volvulus with a jejunal trichobezoar.

BACKGROUND: Small bowel volvulus caused by a jejunal trichobezoar is an extremely rare and life-threatening emergency in children. CASE CHARACTERISTICS: An 8-year-old girl with abdominal pain and persistent bilious vomiting. OBSERVATION: The abdominal computed tomography scan showed a solitary intraluminal mass and a whirl sign, suggesting the small bowel volvulus. Emergency laparoscopic exploration revealed the rotated segment of small bowel loops by a jejunal trichobezoar. OUTCOME: Satisfactory recovery after surgery. MESSAGE: Trichobezoars should be considered in the differential diagnosis of abdominal pain and projectile vomiting in children.

FOXP3+ regulatory T cells in children with helicobacter pylori infection.

Despite an intensive pro-inflammatory response, the immune system is unable to clear the organism in Helicobacter pylori gastritis. Regulatory T (Treg) cells, which suppress the immune response of antigen-specific T cells, have recently been demonstrated to play a key role in chronic inflammation by immunologic tolerance. The purpose of our study was to investigate the histopathology, FOXP3+CD4+CD25(high)Treg (FOXP3+Treg) cell expression, and immune responses in children with H. pylori infection. Twenty-four H. pylori -positive and 24 H. pylori -negative children who underwent esophagogastroduodenoscopy for dyspeptic symptoms were included. Histopathologic grading according to the updated Sydney classification and immunohistochemical stains for FOXP3, transforming growth factor-ß1 (TGF-ß1), and CD4 were performed. Histopathologic bacterial density score, gastritis activity score, and chronic inflammation score were higher in the H. pylori -positive group than in the negative group (P < 0.01). The number of FOXP3+Treg cells and CD4+T cells and the grade of TGF-ß1 expression were significantly increased in the H. pylori -positive group compared to the negative group (P < 0.01). The number of FOXP3+Treg cells correlated positively with the grade of TGF-ß1 expression regardless of H. pylori status (P < 0.05). The number of FOXP3+Treg cells and the grade of TGF-ß1 expression correlated positively with H. pylori density, gastritis activity score, and chronic inflammation score regardless of H. pylori status (P < 0.01). These findings indicate that FOXP3+Treg cells could play a role in persistent H. pylori infection.

Successful combined treatment with total parenteral nutrition fluid extravasation injuries in preterm infants.

Extravasation injuries in the neonatal intensive care unit are not rare during parenteral hyperalimentation. There have been many different methods of management. We report five premature infants with wounds of hyperalimentation fluid extravasation managed by the antibacterial ointment (Terramycin ophthalmic ointment and sesame oil and a antiinflammatory herbal mixture (MEBO).) The mean gestational age of patients was 31(+2) weeks (range, 28(+4) to 35(+6) weeks), and the mean weight at extravasation was 1,930 g (range, 1,140 to 2,680 g). Extravasation occurred within the mean of 32 days (range, 17 to 50 days). The method of dressing was application of a thick layer of this mixture covered by vaseline and wet gauze renewed at an interval of 8-12 hr after irrigating the wounds thoroughly with normal saline. The mean duration of dressing was 30 days (range, 20-50 days). The wounds had healed completely leaving a small size of contracture without functional abnormality. We conclude that this therapy may be considered for an alternative treatment and warrants clinical trials for the confirmation of the local management of extravasation injury.