Effects of Soluble Dextrin Fiber from Potato Starch on Body Weight and Associated Gut Dysbiosis Are Evident in Western Diet-Fed Mice but Not in Overweight/Obese Children.

BACKGROUND: The study investigated the impact of starch degradation products (SDexF) as prebiotics on obesity management in mice and overweight/obese children. METHODS: A total of 48 mice on a normal diet (ND) and 48 on a Western diet (WD) were divided into subgroups with or without 5% SDexF supplementation for 28 weeks. In a human study, 100 overweight/obese children were randomly assigned to prebiotic and control groups, consuming fruit and vegetable mousse with or without 10 g of SDexF for 24 weeks. Stool samples were analyzed for microbiota using 16S rRNA gene sequencing, and short-chain fatty acids (SCFA) and amino acids (AA) were assessed. RESULTS: Results showed SDexF slowed weight gain in female mice on both diets but only temporarily in males. It altered bacterial diversity and specific taxa abundances in mouse feces. In humans, SDexF did not influence weight loss or gut microbiota composition, showing minimal changes in individual taxa. The anti-obesity effect observed in mice with WD-induced obesity was not replicated in children undergoing a weight-loss program. CONCLUSIONS: SDexF exhibited sex-specific effects in mice but did not impact weight loss or microbiota composition in overweight/obese children.

Quantitative digital pathology enables automated and quantitative assessment of inflammatory activity in patients with autoimmune hepatitis.

Background: Chronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component. Methods: Whole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC). Results: ID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation. Conclusion: Quantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.

Pediatricians' practices and knowledge of metabolic dysfunction-associated steatotic liver disease: An international survey.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in children. It is associated with significant intra- and extrahepatic comorbidity. Current guidelines lack consensus, potentially resulting in variation in screening, diagnosis and treatment practices, which may lead to underdiagnosing and/or insufficient treatment. The increasing prevalence of MASLD and associated long-term health risks demand adequate clinical management and consensus in guidelines. This study aims to evaluate the daily practices of pediatricians in screening, diagnosis and treatment of MASLD in children. METHODS: An online survey with 41 questions (single/multiple response options) was sent to pediatricians (with/without subspecialty) in Europe and Israel, via members of the ESPGHAN Fatty Liver Special Interest Group, between June and November 2022. The 454 pediatricians were included in this study. RESULTS: 51% of pediatricians indicated using any guideline for diagnosis and treatment of MASLD, with 68% reporting to follow recommendations only partially. 63% is of the opinion that guidelines need revision. The majority of pediatricians screen for MASLD with liver function tests and/or abdominal ultrasound. A large variety of treatment options is utilized, including lifestyle management, supplements and probiotics, with a notable 34% of pediatricians prescribing pharmacotherapy. When asked how often pediatricians request a liver biopsy in children with MASLD, 17% indicates they request a liver biopsy in more than 10% of cases. CONCLUSIONS: There is limited awareness and considerable variation in screening, diagnosis and treatment practices among European pediatricians, and a clear demand for new, uniform guidelines for MASLD in children.

Noninvasive scores are poorly predictive of histological fibrosis in paediatric fatty liver disease.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. Roughly a quarter of paediatric patients with NAFLD develop nonalcoholic steatohepatitis and fibrosis. Here, we evaluated the diagnostic accuracy of previously published noninvasive fibrosis scores to predict liver fibrosis in a large European cohort of paediatric patients with NAFLD. METHODS: The 457 patients with biopsy-proven NAFLD from 10 specialized centers were included. We assessed diagnostic accuracy for the prediction of any (F ≥ 1), moderate (F ≥ 2) or advanced (F ≥ 3) fibrosis for the AST/platelet ratio (APRI), Fibrosis 4 score (FIB-4), paediatric NAFLD fibrosis score (PNFS) and paediatric NAFLD fibrosis index (PNFI). RESULTS: Patients covered the full spectrum of fibrosis (F0: n = 103; F1: n = 230; F2: n = 78; F3: n = 44; F4: n = 2). None of the scores were able to accurately distinguish the presence of any fibrosis from no fibrosis. For the detection of moderate fibrosis, area under the receiver operating characteristic curve (AUROC) were: APRI: 0.697, FIB-4: 0.663, PNFI: 0.515, PNFS: 0.665, while for detection of advanced fibrosis AUROCs were: APRI: 0.759, FIB-4: 0.611, PNFI: 0.521, PNFS: 0.712. Fibrosis scores showed no diagnostic benefit over using ALT ≤ 50/ > 50 IU/L as a cut-off. CONCLUSIONS: Established fibrosis scores lack diagnostic accuracy to replace liver biopsy for staging of fibrosis, giving similar results as compared to using ALT alone. New diagnostic tools are needed for Noninvasive risk-stratification in paediatric NAFLD.

Are children with gallstone disease more overweight? Results of a matched case-control analysis.

INTRODUCTION: Gallstone disease (GD) is increasingly common among children, possibly caused by an unhealthy food environment and the associated unhealthy lifestyle. In this study, we investigate the association between body weight and gallstone risk in a cohort of prospectively recruited children with GD. METHODS: We analysed 188 children with gallstones (50.0% girls, median age 9.8 years) and 376 children without stones who were age- and gender-matched to cases in a ratio of 2:1. Cases were prospectively recruited at three Polish university centres (Warsaw, Katowice and Bialystok). Gallstones were diagnosed by either abdominal sonography or by a history of cholecystectomy. Matched controls without gallstones were selected from 22,412 children taking part in nationally representative Polish health surveys (OLA and OLAF studies) which provided height and weight data for randomly selected pre-school (2.5-6 years) and school aged (7-18 years) children and adolescents. RESULTS: Analysis of the age- and gender-matched cases and controls demonstrated that patients with GD had significantly higher BMI (P = 0.02) and BMI z-score (P < 0.01) than children without stones. Children with gallstones were more frequently overweight (35.6%, P < 0.01) and obese (12.2%, P < 0.01) than controls (18.4% and 6.7%, respectively). Regression analyses showed that BMI, BMI z-score, overweight and obesity were all associated with increased GD risk (all P < 0.05). CONCLUSIONS: Overweight and obesity are common in children with cholelithiasis. Given the epidemic of obesity in children we should expect an increasing prevalence of gallstones and stone-related complications in youths and in adults.

Relationship of gut microbiota and immunological response in obesity-related non-alcoholic fatty liver disease in children.

In the development of NAFLD plays an important role the intestinal microflora. Our aim was to characterize role microbiota in children. Distinctive gut microbiota composition was observed in children, characterized and short-chain fatty acid producing bacteria. For the treatment of NAFLD it is possible by therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain the integrity of the intestinal barrier are potential agents.

Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) arises due to inherited variants in SERPINA1, the AAT gene that impairs the production or secretion of this hepatocellular protein and leads to a gain-of-function liver proteotoxicity. Homozygous Pi*Z pathogenic variant (Pi*ZZ genotype) is the leading cause of severe AATD. It manifests in 2 to 10% of carriers as neonatal cholestasis and 20 to 35% of adults as significant liver fibrosis. Both children and adults may develop an end-stage liver disease requiring liver transplantation. Heterozygous Pi*Z pathogenic variant (Pi*MZ genotype) constitutes an established disease modifier. Our review summarizes the natural history and management of subjects with both pediatric and adult AATD-associated liver disease. Current findings from a phase 2 clinical trial indicate that RNA silencing may constitute a viable therapeutic approach for adult AATD. In conclusion, AATD is an increasingly appreciated pediatric and adult liver disorder that is becoming an attractive target for modern pharmacologic strategies.

Infant and Young Child Feeding Practices and Health.

Early childhood feeding practices are fundamental for a child's healthy growth, development and potential [...].

Shiga Toxin-Producing Escherichia coli in Faecal Samples from Wild Ruminants.

Wildlife can harbour Shiga toxin-producing Escherichia coli (STEC). In the present study, STEC in faecal samples from red deer (n = 106) and roe deer (n = 95) were characterised. All isolates were non-O157 strains. In red deer, STEC were detected in 17.9% (n = 19) of the isolates, and the eae/stx2b virulence profile was detected in two isolates (10.5%). One STEC strain harboured stx1a (5.3%) and eighteen STEC strains harboured stx2 (94.7%). The most prevalent stx2 subtypes were stx2b (n = 12; 66.7%), stx2a (n = 3; 16.7%), and stx2g (n = 2; 11.1%). One isolate could not be subtyped (NS) with the applied primers (5.6%). The most widely identified serotypes were O146:H28 (n = 4; 21%), O146:HNM (n = 2; 10.5%), O103:H7 (n = 1; 5.3%), O103:H21 (n = 1; 5.3%), and O45:HNM (n = 1; 5.3%). In roe deer, STEC were detected in 16.8% (n = 16) of the isolates, and the eae/stx2b virulence profile was detected in one isolate (6.3%). Two STEC strains harboured stx1a (12.5%), one strain harboured stx1NS/stx2b (6.3%), and thirteen strains harboured stx2 (81.3%). The most common subtypes were stx2b (n = 8; 61.5%), stx2g (n = 2; 15.4%), non-typeable subtypes (NS) (n = 2; 15.4%), and stx2a (n = 1; 7.7%). Serotype O146:H28 (n = 5; 31.3%) was identified. The study demonstrated that the zoonotic potential of STEC strains isolated from wildlife faeces should be monitored in the context of the 'One Health' approach which links human health with animal and environmental health.

Comparison of the Activity of Fecal Enzymes and Concentration of SCFA in Healthy and Overweight Children.

In modern societies obesity has become a serious issue which must be urgently addressed. The health implications of neglected obesity are substantial, as not only does it affect individuals' everyday lives, but it also leads to significantly increased mortality due to the development of several disorders such as type-2 diabetes, cardiovascular diseases, cancers, and depression. The objective of this research was to investigate the alterations in selected health markers caused by overweight and obesity in children. The measured parameters were the activity of the fecal enzymes, the concentration of short-chain fatty acids (SCFAs), and the concentration of branched-chain fatty acids (BCFAs). The activity of the fecal enzymes, specifically α-glucosidase, α-galactosidase, ß-glucosidase, ß-galactosidase, and ß-glucuronidase, was determined using spectrophotometry at a wavelength of 400 nm. Furthermore, concentrations of lactic acid, SCFAs (formic, acetic, propionic, butyric, and valeric acids), and BCFAs (isobutyric and isovaleric acids) were determined using the HPLC method. The obtained results reveal that obese children have different fecal enzyme activity and a different profile of fatty acids from children of normal weight. The group of obese children, when compared to children of normal weight, had increased concentrations of BCFAs (p < 0.05) and higher activity of potentially harmful enzymes such as ß-glucosidase and ß-glucuronidase (p < 0.05). In comparison, children of normal weight exhibited significantly increased concentrations of lactic acid and SCFAs (especially formic and butyric acids) (p < 0.05). Furthermore, their α-glucosidase and α-galactosidase activity were higher when compared to the group of obese children (p < 0.05). These results suggest that the prevalence of obesity has a significant impact on metabolites produced in the gastrointestinal tract, which might result in a higher chance of developing serious diseases.

Prevalence and Significance of Autoantibody Seropositivity in Children with Wilson's Disease.

Autoantibodies occur in healthy subjects as well as in children with Wilson's disease (WD), but their prevalence and significance are unknown. Thus, we aimed to assess the prevalence of autoantibodies and autoimmune markers, and their relationship to liver injury in WD children. The study included 74 WD and 75 healthy children as a control group. Patients with WD underwent transient elastography (TE) examinations, as well as determination of liver function tests, copper metabolism markers, and serum immunoglobulins (Ig). In the sera of the WD patients and controls, anti-nuclear (ANA), anti-smooth muscle, anti-mitochondrial, anti-parietal cell, anti-liver/kidney microsomal, anti-neutrophil cytoplasmic autoantibodies, and specific celiac antibodies were determined. Among the autoantibodies, only the prevalence of ANA in children with WD was higher than in the controls. There was no significant relationship between the presence of autoantibodies and liver steatosis or stiffness after TE. However, advanced liver stiffness (E > 8.2 kPa) was related to IgA, IgG, and gamma globulin production. The type of treatment did not influence the prevalence of autoantibodies. Our results suggest that autoimmune disturbances in WD might not be directly related to liver damage as expressed by steatosis and/or liver stiffness after TE.

Phase III Randomized Non-Inferiority Study of OSS Versus PEG + Electrolyte Colonoscopy Preparation in Adolescents.

OBJECTIVES: Many protocols and preparations are used for bowel cleansing before pediatric colonoscopy but few are based on scientific evidence. We evaluated efficacy, safety, tolerability, and patient preference of oral sulfate solution (OSS) at 75% of the adult dose versus polyethylene glycol (PEG)-electrolyte solution in adolescents presenting for diagnostic colonoscopy. METHODS: Phase III, randomized, evaluator-blinded, non-inferiority study of OSS and PEG in adolescents aged 12-17 years. OSS and PEG were administered in 2 doses on the day before colonoscopy. Primary endpoint included proportion of patients with successful overall preparation (4-point scale). Secondary endpoints included overall and segmental bowel cleansing (Boston Bowel Preparation Scale; BBPS), completed colonoscopies, duration of examination, time to cecal intubation, proportion of nasogastric tubes (NGTs), adverse events (AEs) and acceptability. RESULTS: Successful cleansing was achieved in 71.4% and 79.0% of patients receiving OSS and PEG, respectively [adjusted difference -7.61 (95% confidence interval, CI, -18.45 to 3.24); P = 0.0907]. Segmental BBPS score for the left and transverse colon were similar between treatment groups, but better for the right colon with PEG than OSS [2.2 (95% CI, 2.0-2.4) and 1.9 (95% CI, 1.7-2.1), respectively; P = 0.0015]. Significantly fewer OSS patients needed NGT placement to ingest the whole solution [9/125 (7.2%)] than PEG patients [36/116 (31.0%); P < 0.0001]. Treatment acceptability was significantly higher with OSS than PEG ( P < 0.0001). Duration of examination, completed colonoscopies, and time to cecal intubation were similar between preparations. Gastrointestinal AEs including nausea, vomiting, abdominal pain, and distension were similar in both groups but more patients receiving PEG had AEs assessed as incapacitating. CONCLUSIONS: Non-inferiority of OSS to PEG was not demonstrated, but OSS was associated with a lower requirement for NGT, better acceptability, and less frequent severe AEs than with PEG.

Position statement of the Polish Academy of Sciences Committee Human Nutrition Science on the principles for the nutrition of children aged 1-3 years.

The Position Statement on the principles of nutrition for children aged 1-3 years emphasizes that proper nutrition of children at this age determines their optimal psychometric development and has beneficial effects on the process nutritional programming, which reduces the risk of diet-related diseases in adulthood. Continued breastfeeding in the post-infancy period, together with the proper introduction of complementary foods, supplies all the nutritional needs of the child. A varied selection of food products is important to balance out the diet of a child in the context of energy and nutrient needs. Attention should be paid to products not recommended for frequent consumption, due to the possibility of the early development of improper eating habits that can lead to undesirable health consequences. Due to the potential risk of deficiency, adequate intake of iron, iodine, calcium and vitamin D, as well as of n-3 PUFAs (which is often insufficient) should be provided. Adequate dietary energy and protein intake protects children against protein-energy undernutrition and is crucial for their proper growth and development. An important element in the assessment of the development of children involves monitoring their nutritional status and physical development by systematically measuring their body weight and length/height and analyzing their weight gain. It is necessary to diagnose the causes of being underweight/overweight in children. Physical activity (such as outdoor walks, plays, and games) and healthy sleep hygiene are recommended. Physical activity, an adequate number of hours of sleep, and the quality of sleep in early childhood may improve immunity, reduce the risk of excessive weight gain, and consequently reduce the risk of obesity later in life. Other issues discussed include the functioning of the digestive system as one of the determinants of the nutrition of young children, basics of proper nutrition, risk of nutrient deficiencies and development of proper eating habits in early childhood.

Different protein intake in the first year and its effects on adiposity rebound and obesity throughout childhood: 11 years follow-up of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Infant feeding affects child growth and later obesity risk. We examined whether protein supply in infancy affects the adiposity rebound, body mass index (BMI) and overweight and obesity up to 11 years of age. METHODS: We enrolled healthy term infants from five European countries in a double blind randomized trial, with anticipated 16 examinations within 11 years follow-up. Formula-fed infants (n = 1090) were randomized to isoenergetic formula with higher or lower protein content within the range stipulated by EU legislation in 2001. A breastfed reference group (n = 588) was included. Adiposity rebound and BMI trajectories were estimated by generalized additive mixed models in 917 children, with 712 participating in the 11 year follow-up. RESULTS: BMI trajectories were elevated in the higher compared to the lower protein group, with significantly different BMI at adiposity rebound (0.24 kg/m2, 0.01-0.47, p = 0.040), and an increased risk for overweight at 11 years (adjusted Odds Ratio 1.70; 1.06-2.73; p = 0.027) but no significant difference for obesity (adjusted Odds Ratio 1.47; 0.66-3.27). The two formula groups did not differ in the timing of adiposity rebound, but all children with obesity at 11 years had an early adiposity rebound before four years. CONCLUSIONS: Compared to conventional high protein formula, feeding lower protein formula in infancy lowers BMI trajectories up to 11 years and achieves similar BMI values at adiposity rebound as observed in breastfed infants.

Time of Dietary Energy and Nutrient Intake and Body Mass Index in Children: Compositional Data Analysis from the Childhood Obesity Project (CHOP) Trial.

Meal timing is suggested to influence the obesity risk in children. Our aim was to analyse the effect of energy and nutrient distributions at eating occasions (EO), including breakfast, lunch, supper, and snacks, on the BMI z-score (zBMI) during childhood in 729 healthy children. BMI and three-day dietary protocols were obtained at 3, 4, 5, 6, and 8 years of age, and dietary data were analysed as the percentage of the mean total energy intake (TEI; %E). Intakes at EOs were transformed via an isometric log-ratio transformation and added as exposure variables to linear mixed-effects models. Stratified analyses by country and recategorization of EOs by adding intake from snacks to respective meals for further analyses were performed. The exclusion of subjects with less than three observations and the exclusion of subjects who skipped one EO or consumed 5% energy or less at one EO were examined in sensitivity analyses. Around 23% of the children were overweight at a given time point. Overweight and normal-weight children showed different distributions of dietary intakes over the day; overweight children consumed higher intakes at lunch and lower intakes of snacks. However, no significant effects of timing of EOs on zBMI were found in regression analyses.

The rs12532734 Polymorphism Near the Solute Carrier 26A3 Gene Locus Is Associated With Gallstone Disease in Children.

Gallstones are increasingly frequent in children. In this candidate gene study, we genotyped 5 gene variants ( ANO1 , SPTLC3 , TMEM147 , TNRC6B , rs12532734) from a recent gallstone genome-wide association study (GWAS) in a cohort of 214 children with gallstones and 172 gallstone-free adult controls. In total, 138 genotyped children presented with symptomatic gallstone disease, 47 underwent cholecystectomy, and 126 received ursodeoxycholic acid (UDCA) as therapy for stones. Among 5 tested variants, the rs12532734 polymorphism modulated the gallstone risk in the studied cohort. Its genotype distribution significantly ( P = 0.025) departed from the Hardy-Weinberg equilibrium among cases, and the common allele was associated with increased odds of developing gallstones at young age (OR = 1.69, P = 0.014). SLC26A3 is the nearest gene to rs12532734 and is involved in the transepithelial bicarbonate and chloride transport. The association of rs12532734 with pediatric gallstones is a novel finding warranting further investigations also with regard to biliary bicarbonate flux and bile composition.

Childhood Obesity: Position Statement of Polish Society of Pediatrics, Polish Society for Pediatric Obesity, Polish Society of Pediatric Endocrinology and Diabetes, the College of Family Physicians in Poland and Polish Association for Study on Obesity.

Childhood obesity is one of the most important problems of public health. Searching was conducted by using PubMed/MEDLINE, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases, from January 2022 to June 2022, for English language meta-analyses, systematic reviews, randomized clinical trials, and observational studies from all over the world. Five main topics were defined in a consensus join statement of the Polish Society of Pediatrics, Polish Society for Pediatric Obesity, Polish Society of Pediatric Endocrinology and Diabetes and Polish Association for the Study on Obesity: (1) definition, causes, consequences of obesity; (2) treatment of obesity; (3) obesity prevention; (4) the role of primary care in the prevention of obesity; (5) Recommendations for general practitioners, parents, teachers, and regional authorities. The statement outlines the role of diet, physical activity in the prevention and treatment of overweight and obesity, and gives appropriate recommendations for interventions by schools, parents, and primary health care. A multisite approach to weight control in children is recommended, taking into account the age, the severity of obesity, and the presence of obesity-related diseases. Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education are effective in improving metabolic and anthropometric indices. More actions are needed to strengthen the role of primary care in the effective prevention and treatment of obesity because a comprehensive, multi-component intervention appears to yield the best results.

Quantitative MR in Paediatric Patients with Wilson Disease: A Case Series Review.

Wilson disease (WD) is a liver disorder characterized by improper copper metabolism. Although non-invasive tools are currently used to support diagnosis and management, this is still an area of unmet need, as patients present with a wide range of symptoms. Our aim was to investigate the potential utility of multiparametric magnetic resonance imaging (mpMRI) and quantitative magnetic resonance cholangiopancreatography (MRCP+) to support patient management. MRI examinations of 7 children and young adults aged 8-16 years (six at diagnosis) were performed alongside a standard of care clinical and histological examination. Images were quantitatively analyzed to derive metrics of liver (corrected T1 (cT1; fibro-inflammation), MR liver fat (proton density fat fraction; PDFF)), and biliary health (MRCP+). MRI-PDFF provided a more dynamic characterization of fat compared with that provided by ultrasound. Those with elevated histological scores of fibrosis, inflammation, and steatosis had elevated mpMRI values. MRCP+ managed to identify dilatations in the biliary tree which were not observed during the standard of care examination. mpMRI and MRCP+ metrics show early promise as markers to assess both liver and biliary health in Wilson disease. Investigations to understand and explore the utility of these markers are warranted and should be performed.