Impact of Extreme Obesity and Diet-Induced Weight Loss on the Fecal Metabolome and Gut Microbiota

Scope: A limited number of human studies have characterized fecal microbiota and metabolome in extreme obesity and after diet-induced weight loss. Methods and results: Fecal samples from normal-weight and extremely obese adults and from obese participants before and after moderate diet-induced weight loss are evaluated for their interaction with the intestinal adenocarcinoma cell line HT29 using an impedance-based in vitro model, which reveals variations in the interaction between the gut microbiota and host linked to obesity status. Microbiota composition, short chain fatty acids, and other intestinal metabolites are further analyzed to assess the interplay among diet, gut microbiota, and host in extreme obesity. Microbiota profiles are distinct between normal-weight and obese participants and are accompanied by fecal signatures in the metabolism of biliary compounds and catecholamines. Moderate diet-induced weight loss promotes shifts in the gut microbiota, and the primary fecal metabolomics features are associated with diet and the gut–liver and gut–brain axes. Conclusions: Analyses of the fecal microbiota and metabolome enable assessment of the impact of diet on gut microbiota composition and activity, supporting the potential use of certain fecal metabolites or members of the gut microbiota as biomarkers for the efficacy of weight loss in extreme obesity

In vitro evaluation of different prebiotics on the modulation of gut microbiota composition and function in morbid obese and normal-weight subjects

The gut microbiota remains relatively stable during adulthood; however, certain intrinsic and environmental factors can lead to microbiota dysbiosis. Its restoration towards a healthy condition using best-suited prebiotics requires previous development of in vitro models for evaluating their functionality. Herein, we carried out fecal cultures with microbiota from healthy normal-weight and morbid obese adults. Cultures were supplemented with different inulin-type fructans (1-kestose, Actilight, P95, Synergy1 and Inulin) and a galactooligosaccharide. Their impact on the gut microbiota was assessed by monitoring gas production and evaluating changes in the microbiota composition (qPCR and 16S rRNA gene profiling) and metabolic activity (gas chromatography). Additionally, the effect on the bifidobacterial species was assessed (ITS-sequencing). Moreover, the functionality of the microbiota before and after prebiotic-modulation was determined in an in vitro model of interaction with an intestinal cell line. In general, 1-kestose was the compound showing the largest effects. The modulation with prebiotics led to significant increases in the Bacteroides group and Faecalibacterium in obese subjects, whereas in normal-weight individuals, substantial rises in Bifidobacterium and Faecalibacterium were appreciated. Notably, the results obtained showed differences in the responses among the tested compounds but also among the studied human populations, indicating the need for developing population-specific products

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform

The aim of this study was to validate the Lipochip genetic diagnostic platform by assessing effectiveness, sensitivity, specificity and costs for the identification of patients with familial hypercholesterolemia (FH) in Spain. This platform includes the use of a DNA micro array, the detection of large gene rearrangements and the complete resequencing of the low-density lipoprotein receptor gene. DNA samples of patients with clinically diagnosed FH were analyzed for mutations by application of the Lipochip platform. Results obtained were confirmed by DNA sequencing and MLPA analysis by two other, independent laboratories. Of 808 patients tested, Lipochip detected a mutation in 66% of the cases and of these 78% were detected by the micro array. A specificity of 99.5% at a sensitivity of 99.8% was reached. A positive test result could be reported within 22 days after start of analysis. The total average screening costs of $350 per case were significantly lower compared to other existing screening programs. Lipochip provides a reliable, fast and cheap alternative for the genetic testing of patients with clinically diagnosed F

Nutrición parenteral domiciliaria en españa 2017. Informe del grupo de nutrición artificial domiciliaria y ambulatoria NADYA

Aim: to communicate HPN data obtained from the HPN registry of the NADYA-SENPE group (www.nadya-senpe.com) for the year 2017. Material and methods: descriptive analysis of the data collected from adult and pediatric patients with HPN in the NADYA-SENPE group registry from January 1st, 2017 to December 31st, 2017. Results: there were 308 patients from 45 Spanish hospitals (54.5% women), 38 children and 270 adults, with 3,012 episodes, which represent a prevalence rate of 6.61 patients/million inhabitants/year 2017. The most frequent diagnosis in adults was "palliative cancer" (25.6%), followed by "others". In children, it was Hirschsprung's disease with six cases (15.8%). The first indication was short bowel syndrome in both children (55.3%) and adults (33.7%). The most frequently used type of catheter was tunneled in both children (73.4%) and adults (38.2%). Ending 81 episodes, the most frequent cause was death (62.9%) and transition to oral feeding (34.7%). Conclusions: the progressive increase of collaborating centers and professionals in the registry of patients receiving NPD is maintained. The main indications of HPN and the motive for ending have remained stable

Dissecting neural differentiation regulatory networks through epigenetic footprinting

Human pluripotent stem cell derived models that accurately recapitulate neural development in vitro and allow for the generation of specific neuronal subtypes are of major interest to the stem cell and biomedical community. Notch signaling, particularly through the Notch effector HES5, is a major pathway critical for the onset and maintenance of neural progenitor cells (NPCs) in the embryonic and adult nervous system(1-3). This can be exploited to isolate distinct populations of human embryonic stem (ES) cell derived NPCs(4). Here, we report the transcriptional and epigenomic analysis of six consecutive stages derived from a HES5-GFP reporter ES cell line(5) differentiated along the neural trajectory aimed at modeling key cell fate decisions including specification, expansion and patterning during the ontogeny of cortical neural stem and progenitor cells. In order to dissect the regulatory mechanisms that orchestrate the stage-specific differentiation process, we developed a computational framework to infer key regulators of each cell state transition based on the progressive remodeling of the epigenetic landscape and then validated these through a pooled shRNA screen. We were also able to refine our previous observations on epigenetic priming at transcription factor binding sites and show here that they are mediated by combinations of core and stage- specific factors. Taken together, we demonstrate the utility of our system and outline a general framework, not limited to the context of the neural lineage, to dissect regulatory circuits of differentiation