RESUMEN
BACKGROUND: Probiotics may provide a benefit for adults with Prader-Willi syndrome (PWS) experiencing constipation. The primary aim was to determine if Bifidobacterium animalis ssp. lactis B94 (B. lactis B94) improves stool frequency, with secondary aims of stool form and gastrointestinal symptoms. Exploratory aims included diet quality and fecal microbiota composition. METHODS: Following a 4-week baseline, 25 adults with PWS were randomized to consume B. lactis B94 by capsule (15 billion) or placebo for 4 weeks, followed by 4-week washout in a double-blind, crossover design. Stool frequency and Bristol Stool Form (BSF) were assessed daily, and Gastrointestinal Symptom Rating Scale (GSRS) and dietary intake (7-days food records), per period. Fecal microbiota per period was analyzed using 16S rRNA gene amplicon sequencing and taxa of interest by qPCR (n = 24). RESULTS: No adverse events were reported. Stool frequency at baseline (n = 25; 2.0 ± 0.1 stools/day), GSRS syndromes, and microbiota composition did not differ with the probiotic intervention overall; however, a delayed, carry-over effect on BSF types 6 and 7 was seen. Diet quality by HEI-2015 was 65.4 ± 8.5. CONCLUSION: In adults with PWS, B. lactis B94 exhibited little effect on laxation over 4 weeks; however, further research is needed.
Asunto(s)
Estreñimiento/terapia , Microbioma Gastrointestinal , Síndrome de Prader-Willi/terapia , Probióticos/uso terapéutico , Adulto , Bifidobacterium animalis/patogenicidad , Estreñimiento/etiología , Estreñimiento/microbiología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/microbiologíaRESUMEN
Although gut microbiota has been suggested to play a role in disease phenotypes of Prader-Willi syndrome (PWS), little is known about its composition in affected children and how it relates to hyperphagia. This cross-sectional study aimed to characterize the gut bacterial and fungal communities of children with PWS, and to determine associations with hyperphagia. Fecal samples were collected from 25 children with PWS and 25 age-, sex-, and body mass index-matched controls. Dietary intake data, hyperphagia scores, and relevant clinical information were also obtained. Fecal bacterial and fungal communities were characterized by 16S rRNA and ITS2 sequencing, respectively. Overall bacterial α-diversity and compositions of PWS were not different from those of the controls, but 13 bacterial genera were identified to be differentially abundant. Interestingly, the fungal community, as well as specific genera, were different between PWS and controls. The majority of the variation in the gut microbiota was not attributed to differences in dietary intake or the impact of genotype. Hyperphagia scores were associated with fungal α-diversity and relative abundance of several taxa, such as Staphylococcus, Clostridium, SMB53, and Candida. Further longitudinal studies correlating changes in the microbiome with the degree of hyperphagia and studies integrating multi-omics data are warranted.
Asunto(s)
Microbioma Gastrointestinal , Síndrome de Prader-Willi/microbiología , Candida/genética , Candida/patogenicidad , Niño , Clostridium/genética , Clostridium/patogenicidad , Humanos , Síndrome de Prader-Willi/patología , ARN Ribosómico 16S/genética , Staphylococcus/genética , Staphylococcus/patogenicidadRESUMEN
Prader-Willi syndrome is a rare genetic disorder associated with impaired body composition, hyperphagia, and excessive weight gain. Strict dietary restrictions from an early age is crucial to prevent or delay the early onset of obesity, which is the main driver of comorbidities in these patients. The aim of this study was to identify dietary and gut microbiota components closely linked to weight status of these patients. We studied a cohort of children and adolescents with genetic diagnosis of Prader-Willi syndrome (N = 31), in which we determined adiposity by Dual-energy X-ray absorptiometry (DXA) and dietary composition with 4-day food records. Furthermore, we obtained fecal samples to assess microbiota composition by 16S sequencing. Multivariate regression models showed that body mass index standard deviation score (BMI-SDS) and body fat mass were directly associated with saturated fat intake and meat consumption, and inversely associated with fruit consumption. Furthermore, the gut microbiome from normal weight patients was characterized by higher phylogenetic diversity compared to those overweight or obese, with differential abundance of several genera, including Alistipes, Klebsiella, and Murimonas. Notably, Alistipes abundance was inversely correlated to adiposity, lipid and glucose homeostasis parameters, and meat intake. Our results suggest that limiting meat and increasing fruit intake might be beneficial for body weight management in children and adolescents with Prader-Willi syndrome.
Asunto(s)
Grasas de la Dieta/efectos adversos , Frutas , Microbioma Gastrointestinal , Carne/efectos adversos , Obesidad Infantil/dietoterapia , Obesidad Infantil/prevención & control , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/microbiología , Adolescente , Distribución de la Grasa Corporal , Índice de Masa Corporal , Mantenimiento del Peso Corporal , Niño , Preescolar , Femenino , Humanos , Masculino , Obesidad Infantil/etiología , Obesidad Infantil/microbiologíaRESUMEN
OBJECTIVE: The gut microbiota has been implicated in the aetiology of obesity and associated comorbidities. Patients with Prader-Willi syndrome (PWS) are obese but partly protected against insulin resistance. We hypothesised that the gut microbiota of PWS patients differs from that of non-genetically obese controls and correlate to metabolic health. Therefore, here we used PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity. DESIGN: We conducted a case-control study with 17 adult PWS patients and 17 obese subjects matched for body fat mass index, gender and age. The subjects were metabolically characterised and faecal microbiota was profiled by 16S ribosomal RNA gene sequencing. The patients' parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for faecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism. RESULTS: The composition of the faecal microbiota in patients with PWS differed from that of obese controls, and was characterised by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, and decreased abundance of Dorea. Microbial taxa prevalent in the PWS microbiota were associated with markers of insulin sensitivity. Improved insulin resistance of PWS was partly transmitted by faecal microbiota transplantations into germ-free mice. CONCLUSION: The gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from metabolic complications.
Asunto(s)
Microbioma Gastrointestinal , Obesidad/microbiología , Síndrome de Prader-Willi/microbiología , Adulto , Animales , Estudios de Casos y Controles , Trasplante de Microbiota Fecal , Heces/microbiología , Femenino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiología , Glucosa/metabolismo , Humanos , Masculino , Ratones , Obesidad/complicaciones , Obesidad/metabolismo , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/metabolismo , ARN Ribosómico 16S/genéticaRESUMEN
The vast majority of microorganisms on Earth reside in often-inseparable environment-specific communities-microbiomes. Meta-genomic/-transcriptomic sequencing could reveal the otherwise inaccessible functionality of microbiomes. However, existing analytical approaches focus on attributing sequencing reads to known genes/genomes, often failing to make maximal use of available data. We created faser (functional annotation of sequencing reads), an algorithm that is optimized to map reads to molecular functions encoded by the read-correspondent genes. The mi-faser microbiome analysis pipeline, combining faser with our manually curated reference database of protein functions, accurately annotates microbiome molecular functionality. mi-faser's minutes-per-microbiome processing speed is significantly faster than that of other methods, allowing for large scale comparisons. Microbiome function vectors can be compared between different conditions to highlight environment-specific and/or time-dependent changes in functionality. Here, we identified previously unseen oil degradation-specific functions in BP oil-spill data, as well as functional signatures of individual-specific gut microbiome responses to a dietary intervention in children with Prader-Willi syndrome. Our method also revealed variability in Crohn's Disease patient microbiomes and clearly distinguished them from those of related healthy individuals. Our analysis highlighted the microbiome role in CD pathogenicity, demonstrating enrichment of patient microbiomes in functions that promote inflammation and that help bacteria survive it.
Asunto(s)
Metagenómica/métodos , Microbiota , Anotación de Secuencia Molecular/métodos , Algoritmos , Proteínas Bacterianas/fisiología , Niño , Enfermedad de Crohn/microbiología , Humanos , Síndrome de Prader-Willi/microbiología , Alineación de SecuenciaRESUMEN
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.
Asunto(s)
Carbohidratos de la Dieta/administración & dosificación , Disbiosis/dietoterapia , Disbiosis/microbiología , Microbioma Gastrointestinal , Síndrome de Prader-Willi/dietoterapia , Síndrome de Prader-Willi/microbiología , Adolescente , Animales , Antígenos Bacterianos/sangre , Niño , Preescolar , Disbiosis/sangre , Disbiosis/genética , Femenino , Humanos , Masculino , Ratones , Síndrome de Prader-Willi/sangre , Síndrome de Prader-Willi/genéticaRESUMEN
Prader Willi Syndrome (PWS) is a relatively rare neurogenetic illness. It is of interest to dentists for its clinical characteristics. The aim of this study was to evaluate the amount of saliva and the presence of Streptococcus mutans (St mutans) in patients with this syndrome. We measured saliva stimulated by chewing paraffin tablets for 5 minutes, and cultured saliva samples in order to determine the colony-forming units (CFUs) of St mutans. The study was conducted in a group of 10 children with PWS at the Hospital Sant Joan de Déu, Barcelona. Results showed that patients with PWS had lower saliva secretion than considered normal for a standard population and most cultures presented a high number of colony-forming units. We conclude that these patients are likely to present caries, and stress the need to place special emphasis on prevention.