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.
Shifts in gut microbiota and fecal metabolome features associated with the metabolism of biliary compounds and catecholamines are observed between normal weight (NW) and extremely obese (OB) individuals. Moderate weight loss after diet (OB.2) promotes changes in the gut microbiota whereas the fecal metabolomic profile is mainly associated with dietary changes and with the gut‐liver and gut‐brain axes.
Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on attainment of treatment ...targets; large registries that reflect real-life clinical practice can uniquely provide this information.
We sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry.
The SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT).
The study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals.
Despite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals.
The imbalance of the gut microbiota (GM) is known as dysbiosis and is associated with disorders such as obesity. The increasing prevalence of microorganisms harboring antibiotic resistance genes ...(ARG) in the GM has been reported as a potential risk for spreading multi-drug-resistant pathogens. The objective of this work was the evaluation, in a fecal culture model, of different probiotics for their ability to modulate GM composition and ARG levels on two population groups, extremely obese (OB) and normal-weight (NW) subjects. Clear differences in the basal microbiota composition were observed between NW and OB donors. The microbial profile assessed by metataxonomics revealed the broader impact of probiotics on the OB microbiota composition. Also, supplementation with probiotics promoted significant reductions in the absolute levels of
and
genes. Regarding the
gene, a minor but significant decrease in both donor groups was detected after probiotic addition. A negative association between the abundance of Bifidobacteriaceae and the
gene was observed. Our results show the ability of some of the tested strains to modulate GM. Moreover, the results suggest the potential application of probiotics for reducing the levels of ARG, which constitutes an interesting target for the future development of probiotics.
The intestinal microbiota plays important roles in the maintenance of health. Strategies aiming at its modulation, such as probiotics, have received a deal of attention. Several strains have been ...studied in different
models; however, the correlation of results obtained with the
data has been limited. This questions the usefulness of such
selection models, traditionally relying on over-simplified tests, not considering the influence of the accompanying microbiota or focusing on microbiota composition without considering functional traits. Here we assess the potential of six
,
and
strains in an
model to determine their impact on the microbiota not just in terms of composition but also of functionality. Moreover, we compared the responses obtained in two different population groups: normal-weight and severely obese subjects. Fecal cultures were conducted to evaluate the impact of the strains on specific intestinal microbial groups, on the production of short-chain fatty acids, and on two functional responses: the production of gas and the interaction with human intestinal epithelial cells. The response to the different probiotics differed between both human groups. The addition of the probiotic strains did not induce major changes on the microbiota composition, with significant increases detected almost exclusively for the species added. Higher levels of gas production were observed in cultures from normal-weight subjects than in the obese population, with some strains being able to significantly reduce gas production in the latter group. Moreover, in obese subjects all the
strains tested and
GG were able to modify the response of the intestinal cells, restoring values similar to those obtained with the microbiotas of normal-weight subjects. Our results underline the need for the screening and selection of probiotics in a target-population specific manner by using appropriate
models before enrolling in clinical intervention trials.
Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular (CV) disease (ASCVD). However, it still is severely underdiagnosed. ...Initiating lipid-lowering therapy (LLT) in FH patients early in life can substantially reduce their ASCVD risk. As a result, identifying FH is of the utmost importance. The increasing availability of genetic testing may be useful in this regard. We aimed to evaluate the genetic profiles, clinical characteristics, and gender differences between the first consecutive patients referred for genetic testing with FH clinical suspicion in our institution (a Spanish cohort). Clinical information was reviewed, and all participants were sequenced for the main known genes related to FH:
,
,
(heterozygous FH),
(autosomal recessive FH), and two other genes related to hyperlipidaemia (APOE and
). The genetic yield was 32%. Their highest recorded LDLc levels were 294 ± 65 SD mg. However, most patients (79%) were under > 1 LLT medication, and their last mean LDLc levels were 135 ± 51 SD.
c.2389+4A>G was one of the most frequent pathogenic/likely pathogenic variants and its carriers had significantly worse LDLc highest recorded levels (348 ± 61 SD vs. 282 ± 60 SD mg/dL,
= 0.002). Moreover, we identified an homozygous carrier of the pathogenic variant
c.207delC (autosomal recessive FH). Both clinical and genetic hypercholesterolemia diagnosis was significantly established earlier in men than in women (25 years old ± 15 SD vs. 35 years old ± 19 SD,
= 0.02; and 43 ± 17 SD vs. 54 ± 19 SD,
= 0.02, respectively). Other important CV risk factors were found in 44% of the cohort. The prevalence of family history of premature ASCVD was high, whereas personal history was exceptional. Our finding reaffirms the importance of early detection of FH to initiate primary prevention strategies from a young age. Genetic testing can be very useful. As it enables familial cascade genetic testing, early prevention strategies can be extended to all available relatives at concealed high CV risk.
Nutritórax: una complicación infrecuente de la nutrición parenteral Rodríguez Escobedo, Raúl; Martínez Faedo, Ceferino; Lanes Iglesias, Soraya ...
Nutrición hospitalaria : organo oficial de la Sociedad Española de Nutrición Parenteral y Enteral,
12/2020, Letnik:
37, Številka:
6
Journal Article
Odprti dostop
Resumen Introducción: la nutrición parenteral (NP) es una modalidad de soporte nutricional con posibles complicaciones, en parte asociadas al catéter venoso central (CVC). El quilotórax consiste en ...el derrame de líquido linfático de origen intestinal en el espacio pleural. Caso clínico: varón de 57 años ingresado para colecistectomía. Presenta un postoperatorio complicado que requiere reposo digestivo y NP. Posteriormente presenta disnea y dolor torácico con derrame pleural bilateral y pericárdico. Inicialmente se interpretó como un quilotórax, por su aspecto lechoso y su contenido en triglicéridos. La TC confirmó la malposición del CVC con salida de NP a nivel del tronco venoso innominado. Fue intervenido quirúrgicamente, realizándose un lavado del mediastino anterior y la reparación de la perforación. La evolución posterior fue favorable. Discusión: la extravasación de la NP al espacio pleural es una complicación infrecuente pero posible de la administración de NP por vía central. Por tanto, debe tenerse en cuenta en el diagnóstico diferencial.
Nutrithorax: an uncommon complication of parenteral nutrition Rodriguez Escobedo, Raul; Martinez Faedo, Ceferino; Lanes Iglesias, Soraya ...
Nutrición hospitalaria : organo oficial de la Sociedad Española de Nutrición Parenteral y Enteral,
2020-Dec-16, Letnik:
37, Številka:
6
Journal Article
Odprti dostop
Introduction: parenteral nutrition (PN) is commonly used as a nutritional support option. It may cause complications, partly due to a central venous access. Chylothorax is an accumulation of ...lymphatic fluid in the pleural space. Case report: a 57-year-old man was admitted for cholecystectomy. A complicated postoperative period required PN. Cardiorespiratory symptoms started while receiving PN, and a bilateral pleural and pericardial effusion was identified. It was initially interpreted as chylothorax due to its milky appearance and high triglyceride content. A CT scan confirmed a malposition of the CVC with PN leakage at the level of the innominate venous trunk. It was surgically repaired. Discussion: PN leakage is an unusual complication of PN. It should be included in the differential diagnosis of pleural effusion.
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
group and
in obese subjects, whereas in normal-weight individuals, substantial rises in
and
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.
Abstract Background Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on ...attainment of treatment targets; large registries that reflect real-life clinical practice can uniquely provide this information. Objectives We sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry. Methods The SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT). Results The study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals. Conclusions Despite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals.
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