Suppressed inflammation in obese children induced by a high-fiber diet is associated with the attenuation of gut microbial virulence factor genes.

In our previous study, a gut microbiota-targeted dietary intervention with a high-fiber diet improved the immune status of both genetically obese (Prader-Willi Syndrome, PWS) and simple obese (SO) children. However, PWS children had higher inflammation levels than SO children throughout the trial, the gut microbiota of the two cohorts was similar. As some virulence factors (VFs) produced by the gut microbiota play a role in triggering host inflammation, this study compared the characteristics and changes of gut microbial VF genes of the two cohorts before and after the intervention using a fecal metagenomic dataset. We found that in both cohorts, the high-fiber diet reduced the abundance of VF, and particularly pathogen-specific, genes. The composition of VF genes was also modulated, especially for offensive and defensive VF genes. Furthermore, genes belonging to invasion, T3SS (type III secretion system), and adherence classes were suppressed. Co-occurrence network analysis detected VF gene clusters closely related to host inflammation in each cohort. Though these cohort-specific clusters varied in VF gene combinations and cascade reactions affecting inflammation, they mainly contained VFs belonging to iron uptake, T3SS, and invasion classes. The PWS group had a lower abundance of VF genes before the trial, which suggested that other factors could also be responsible for the increased inflammation in this cohort. This study provides insight into the modulation of VF gene structure in the gut microbiota by a high-fiber diet, with respect to reduced inflammation in obese children, and differences in VF genes between these two cohorts.

Effects of Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation in Children and Adolescents with Prader-Willi Syndrome: A Randomized Crossover Trial.

Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by a wide range of clinical manifestations, including obesity, hyperphagia, and behavioral problems. Bifidobacterium animalis subsp. lactis strain BPL1 has been shown to improve central adiposity in adults with simple obesity. To evaluate BPL1's effects in children with PWS, we performed a randomized crossover trial among 39 patients (mean age 10.4 years). Participants were randomized to placebo-BPL1 (n = 19) or BPL1-placebo (n = 20) sequences and underwent a 12-week period with placebo/BPL1 treatments, a 12-week washout period, and a 12-week period with the crossover treatment. Thirty-five subjects completed the study. The main outcome was changes in adiposity, measured by dual-energy X-ray absorptiometry. Secondary outcomes included lipid and glucose metabolism, hyperphagia, and mental health symptoms. Generalized linear modeling was applied to assess differences between treatments. While BPL1 did not modify total fat mass compared to placebo, BPL1 decreased abdominal adiposity in a subgroup of patients older than 4.5 years (n = 28). BPL1 improved fasting insulin concentration and insulin sensitivity. Furthermore, we observed modest improvements in some mental health symptoms. A follow-up trial with a longer treatment period is warranted to determine whether BPL1 supplementation can provide a long-term therapeutic approach for children with PWS (ClinicalTrials.gov NCT03548480).

Single-Case Study of Appetite Control in Prader-Willi Syndrome, Over 12-Years by the Indian Extract Caralluma fimbriata.

This paper reports on the successful management of hyperphagia (exaggerated hunger) in a 14yr-old female with Prader-Willi syndrome (PWS). This child was diagnosed with PWS, (maternal uniparental disomy) at 18 months due to developmental delay, hypertonia, weight gain and extreme eating behaviour. Treatment of a supplement for appetite suppression commenced at 2 years of age. This single-case records ingestion of an Indian cactus succulent Caralluma fimbriata extract (CFE) over 12 years, resulting in anecdotal satiety, free access to food and management of weight within normal range. CFE was administered in a drink daily and dose was slowly escalated by observation for appetite suppression. Rigorous testing determined blood count, vitamins, key minerals, HbA1c, IGF-1 and function of the liver and thyroid all within normal range. The report suggests a strategy for early intervention against hyperphagia and obesity in PWS. This case was the instigator of the successful Australian PWS/CFE pilot and though anecdotal, the adolescent continues to ingest CFE followed by paediatricians at the Royal Children's Hospital Melbourne, Victoria, Australia. Future clinical trials are worth considering, to determine an appropriate dose for individuals with PWS.

[Obesity treatment with liraglutide in a patient with Prader-Willi syndrome: a case report]. / Tratamiento de obesidad con liraglutida en un paciente con síndrome de Prader-Willi: reporte de un caso.

BACKGROUND: Prader-Willi syndrome (PWS) is a major cause of syndromic obesity, caused by deletions on chromosome 15q11-q13. It is characterized by neonatal hypotonia, difficulty in feeding with low birth-weight and subsequent development of hyperphagia, behavioral disorders and obesity. Treatment options for weight control in those patients is limited and there are controversies for a surgical approach. CASE REPORT: we present the case of a patient with PWS who achieved weight loss and control through the use of liraglutide, nutritional therapy and physical activity. DISCUSSION: the treatment of obesity in patients with PWS is challenging and requires an adequate nutritional approach combined with psychological therapy. In those patients that persist with uncontrolled appetite, medications such as metformin or GLP-1 analogs can be used.

Prader-Willi Syndrome - nutritional management in children, adolescents and adults.

Prader-Willi Syndrome is a genetic condition caused by an abnormality of chromosome 15, mostly resulting from a deletion.The prevalence of syndrome in Europe has been reported between 1 in 8,000 to 1 in 45,000 births. Characteristic features of the syndrome include hypotonia, short stature, psychomotor development delay, hypogonadism and progressive, life-threatening obesity. Treatment of Prader-Willi Syndrome consists of intensive rehabilitation, psychologicalcare, speech therapy and also, if patient is fulfilling appropriate criteria, growth hormone treatment. An extremely important element of therapy is also properly planned and implemented nutritional management. Adequate diet prevents the malnutrition in the first stage of life and the development of excessive weight in subsequent years. The aim of this article is to provide practical and accurate guidance on nutritional management and diet therapy for physicians and nutritionists who work with children, adolescents and adults with Prader-Willi Syndrome.

Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.

Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. RESEARCH IN CONTEXT: Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

Prader-Willi syndrome and growth hormone deficiency.

Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.

A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS. METHODS: Sixty-three children, aged 2-10 years, with genetically proven PWS participated in the present study. These children had measurements of body composition by dual-energy X-ray absorptiometry and resting energy expenditure (REE), as well as a 3-day diet history analysis both before and after intervention. Energy calculations were based on the individual's REE, with the recommendation that the macronutrients of the diet consist of 30% fat, 45% carbohydrates and 25% protein, with at least 20 g of fibre per day. RESULTS: Thirty-three families adhered to our dietary recommendations for both energy intake and macronutrient distribution. Those 33 children had lower body fat (19.8% versus 41.9%; P < 0.001) and weight management (body mass index SD score 0.3 versus 2.23; P < 0.001) than those whose parents followed the energy intake recommendations but did not alter the macronutrient composition of the diet. Those who followed our recommendations also had a lower respiratory quotient (0.84 versus 0.95; P = 0.002). CONCLUSIONS: Our recommendation for an energy-restricted diet with a well-balanced macronutrient composition and fibre intake improves both weight and body composition in children with PWS compared to a simple energy-restricted diet.

Nutritional and metabolic findings in patients with Prader-Willi syndrome diagnosed in early infancy.

OBJECTIVE: Early treatment (growth hormone and nutritional support) improves development in infants with Prader-Willi syndrome. This study aimed to evaluate the nutritional and metabolic condition of nine patients who were diagnosed and treated in early infancy. METHODS: Nine patients were hospitalized at the age of \xe2\u20ac\xa810 days to 11 months because of severe feeding difficulties, failure to thrive, or developmental delay. The diagnosis of Prader-Willi syndrome was confirmed by fluorescence in situ hybridization or other molecular genetic techniques. Nutritional and metabolic investigations including urinary organic acid analysis, blood amino acid, and acylcarnitine profiles were performed. RESULTS: The diagnosis was made at the mean age of 6.3 months. A deletion of the paternal gene in the 15q11-13 region was detected in all patients. Eight patients had ketosis, seven had malnutrition, five had hyperammonemia, three had liver dysfunction, three had low blood cholesterol level, and two had hypoglycemia. All patients had reduction of serum multiple amino acids and free carnitine. Significant arginine deficiency was found in all patients. Six patients had mildly elevated blood long-chain and very long-chain acylcarnitine. After supplementation with l-arginine, medium-chain fatty acids, l-carnitine, and vitamins, all patients responded with improvement of motor development and nutritional conditions. Four patients were almost caught up on physical and psychomotor development. CONCLUSIONS: Patients with Prader-Willi syndrome are in bad metabolic condition in the early period. Early diagnosis and individual nutritional interventions may improve the nutritional and developmental progress and decrease death rate in infancy.

A special, strict, fat-reduced, and carbohydrate-modified diet leads to marked weight reduction even in overweight adolescents with Prader-Willi syndrome (PWS).

Hyperphagia is a frequent symptom in patients with Prader-Willi Syndrome (PWS) and results in marked obesity with the risk of metabolic and cardiovascular complications. Previously, we reported that our special diet for PWS patients is effective in the long run, if started early at about 2 years of age. Our objective in this study was to investigate if our special diet is also effective in PWS adolescents who are already overweight. We provided a strict, fat-reduced, and carbohydrate-modified diet, consisting of 10 kcal/cm height, to five adolescents (two female, three male) with PWS. Patients were prospectively followed at our center for 2-6 years. BMI, BMI-SDS, and Weight-for-Height Index were recorded over that period. The special diet was started at a mean age of 16 years (range: 14.1-18.9 years) and initial BMI was 41.3 kg/m(2) (range: 32.4-55.5 kg/m(2)), corresponding to BMI-SDS +3.6 (range: +2.8 to +4.5 SDS). Weight-for-Height Index was 243% (range: 190-339%). After 2 years of the diet, BMI decreased to 33 kg/m(2) (range: 26.7-38 kg/m(2)), as well as BMI-SDS +2.7 (range: 1.7-3.4 SDS) and Weight-for-Height Index to 191% (range: 157-232%); p < 0.01. The special diet was still effective in reducing weight after 4-6 years, with a mean BMI of 30.5 kg/m(2) (range: 24.6-34.5 kg/m(2)) and a mean BMI-SDS of +2.1 (range: 0.7-2.9). We conclude that in a period of 2-6 years, our strict, fat-reduced, and carbohydrate-modified diet, with 10 kcal/cm height, is effective even in adolescents with PWS who are already overweight.

Early diagnosis and multidisciplinary care reduce the hospitalization time and duration of tube feeding and prevent early obesity in PWS infants.

BACKGROUND/AIMS: To describe and evaluate the impact of very early diagnosis and multidisciplinary care on the evolution and care of infants presenting with Prader-Willi syndrome (PWS). METHODS: 19 infants diagnosed with PWS before the second month of life were followed by a multidisciplinary team. Median age at the time of analysis was 3.1 years [range 0.4-6.5]. The data were compared with data collected in 1997 from 113 questionnaires filled out by members of the French PWS Association. The patients from this latter data set were 12.0 years [range 4 months to 41 years] at the time of analysis, with a median age of 36 months at diagnosis. RESULTS: The duration of their hospitalization time was significantly reduced from 30.0 [range 0-670] to 21 [range 0-90] days (p = 0.043). The duration of gastric tube feeding was significantly reduced from 30.5 [range 0-427] to 15 [range 0-60] days (p = 0.017). Growth hormone treatment was started at a mean age of 1.9 +/- 0.5 years in 10 infants and L-thyroxine in 6 infants. Only 1 infant became obese at 2.5 years. CONCLUSION: Early diagnosis combined with multidisciplinary care decreases the hospitalization time, duration of gastric tube feeding and prevents early obesity in PWS infants.

Coping with Prader-Willi syndrome.

Weight- and behavior-control issues are major concerns for parents of a child with Prader-Willi syndrome. However, limited information is available on how families implement the necessary dietary restrictions and the effects of the strategies. This study identified the advice a group of families received regarding weight management, the nutrition concerns they faced and how they coped with these concerns, and the effectiveness of their coping strategies. A 2-step survey methodology was used. Survey 1 identified the strategies parents used to cope with the feeding issues typically presented by children with Prader-Willi syndrome. Survey 2 evaluated the frequency with which these coping strategies were used and their effectiveness. Respondents also provided information on why strategies were not effective. Surveys were mailed to 496 parents/guardians of children (aged 25 years or younger) with Prader-Willi syndrome. A total of 293 (64%) responded. Advice given to families centered on general weight management and dietary guidance. Difficulties centered around coping with food-related behaviors. Coping strategies varied; what worked for 1 family did not necessarly work for another. Participants indicated a desire to share experiences and a need for specific strategies to cope with feeding-behavior difficulties. A few basic behavior-management strategies, including successful use of incentives, responding to misbehavior, rewarding compliance with an exercise program, and modifying the behavior management when indicated, are briefly reviewed.

Growth failure in Prader-Willi syndrome is secondary to growth hormone deficiency.

Growth failure is a recognized feature of the Prader-Willi syndrome (PWS). Despite evidence that hypothalamic dysfunction accompanies the syndrome, the etiology of this growth failure remains controversial because most patients with PWS are obese. In order to contribute to resolution of this controversy, we performed a retrospective analysis of 16 obese and non-obese PWS children. GH deficiency was diagnosed in 12 of the 16 subjects and occurred independently of weight status. All of the non-obese subjects were GH deficient. Of the 4 GH-sufficient children, 2 were moderately obese and 2 were morbidly obese. One of these children had clinical evidence of GH deficiency including a low IGF-1 level. Only one of the children had evidence of GH deficiency and a normal IGF-1 level, a pattern that could be attributable to obesity. We conclude that most short children with PWS have growth hormone deficiency and that this deficiency probably results from hypothalamic dysfunction.

A nutrition survey of and recommendations for individuals with Prader-Willi syndrome who live in group homes.

The purpose of this study was to describe anthropometric data and identify diet-related problems of individuals with Prader-Willi syndrome (PWS) who reside in group homes. A group home is a licensed foster care facility that provides 24-hour care for the developmentally disabled. Questionnaires were sent to dietitians (or the person responsible for nutrition care) of 25 group homes; responses from 18 homes were analyzed. The mean age of residents with PWS was 25 +/- 8.4 years and the mean height was 152.4 +/- 9.7 cm. The mean weight for 19- to 22-year-old men was 75.5 +/- 26.8 kg and that for women of the same age was 74.5 +/- 20 kg. The residents consumed a mean of 1,000 to 1,500 kcal/day. Most of the group homes (n = 16) locked their kitchens at night, and in 12 of the homes stealing and hoarding of food occurred. Pica behavior (eating of nonfoods) was reported in 7 homes. One third of all residents had success in weight loss and were on a maintenance diet, but a major problem was determination of a desirable weight goal. Our key recommendations for dietitians are weigh residents weekly; use the body mass index with prescribed zones for determination of weight goals; monitor change in circumference measurements; follow the guidelines of 7 to 8 kcal/cm of height for weight loss and 10 to 14 kcal/cm of height for weight maintenance; administer 1,000 kcal/day or more and encourage daily aerobic exercise; respect food preferences while adhering to dietary prescriptions; adhere to strict food control procedures; and use nutrition education methods and an interdisciplinary approach for behavior modification.

Short-term infusion of pancreatic polypeptide: effect on children with Prader-Willi syndrome.

Ten children with Prader-Willi syndrome (PWS) were given two 90-min infusions of pancreatic polypeptide (PP) (100 pmol.kg-1.h-1) counterbalanced with two saline infusions. Thirty minutes into each infusion, a 60-min appetite test was given. Tests were done after an overnight fast and 1 h after a 275-kcal breakfast meal. Serum assays for biochemistry, glucose, insulin, C peptide, glucagon, cortisol, and PP were performed at the beginning and end of the infusion. Although infusion of PP increased PP concentrations 10-fold, it did not cause physical signs or symptoms, changes in vital signs, or changes in serum biochemistry. Although the test design was sufficiently sensitive to reveal an effect of the pretest meal on subsequent food intake, there was no difference in eating behavior with the saline and PP infusions. This suggests that a short-term normalization of blood PP concentrations does not correct the excessive food intake.

Interdisciplinary case management: a model for intervention.

Interdisciplinary case management is required when clients present problems that do not fall within the purview of any one discipline. The interdisciplinary approach entails the participation of professional and support staff, along with the client and his/her family, in diagnosis, individual program planning, implementation, and evaluation. For example, interdisciplinary case management for a patient with Prader-Willi syndrome (PWS) results in cost-effective, efficacious treatment. Because of the diversity of symptoms, the treatment of Prader-Willi syndrome must incorporate knowledge and skills from a variety of areas. A model for the interdisciplinary case management of PWS is presented. The model is problem focused and emphasizes goals formulated and acted upon by the disciplines represented on the client's treatment team. Communication and coordination of efforts are central to the utility of the model. Additional benefits of interdisciplinary case management include the opportunity for ongoing education and role expansion of team members.