Mora Murri

Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study

BackgroundA recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level.MethodsA case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction.ResultsThe mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group.ConclusionsThis is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota.

Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers

BACKGROUND Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations. OBJECTIVE The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits. DESIGN Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of de-alcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured. RESULTS The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides-Eubacterium rectale groups (P < 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P < 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number. CONCLUSION This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet. This trial was registered at controlled-trials.com as ISRCTN88720134.

Gut Microbiota Composition in Male Rat Models under Different Nutritional Status and Physical Activity and Its Association with Serum Leptin and Ghrelin Levels

Background Several evidences indicate that gut microbiota is involved in the control of host energy metabolism. Objective To evaluate the differences in the composition of gut microbiota in rat models under different nutritional status and physical activity and to identify their associations with serum leptin and ghrelin levels. Methods In a case control study, forty male rats were randomly assigned to one of these four experimental groups: ABA group with food restriction and free access to exercise; control ABA group with food restriction and no access to exercise; exercise group with free access to exercise and feed ad libitum and ad libitum group without access to exercise and feed ad libitum. The fecal bacteria composition was investigated by PCR-denaturing gradient gel electrophoresis and real-time qPCR. Results In restricted eaters, we have found a significant increase in the number of Proteobacteria, Bacteroides, Clostridium, Enterococcus, Prevotella and M. smithii and a significant decrease in the quantities of Actinobacteria, Firmicutes, Bacteroidetes, B. coccoides-E. rectale group, Lactobacillus and Bifidobacterium with respect to unrestricted eaters. Moreover, a significant increase in the number of Lactobacillus, Bifidobacterium and B. coccoides–E. rectale group was observed in exercise group with respect to the rest of groups. We also found a significant positive correlation between the quantity of Bifidobacterium and Lactobacillus and serum leptin levels, and a significant and negative correlation among the number of Clostridium, Bacteroides and Prevotella and serum leptin levels in all experimental groups. Furthermore, serum ghrelin levels were negatively correlated with the quantity of Bifidobacterium, Lactobacillus and B. coccoides–Eubacterium rectale group and positively correlated with the number of Bacteroides and Prevotella. Conclusions Nutritional status and physical activity alter gut microbiota composition affecting the diversity and similarity. This study highlights the associations between gut microbiota and appetite-regulating hormones that may be important in terms of satiety and host metabolism.

Hemoglobin A1c Versus Oral Glucose Tolerance Test in Postpartum Diabetes Screening

OBJECTIVE To determine the usefulness of measuring hemoglobin A1c (A1C), alone or combined with the fasting glucose test, compared with the oral glucose tolerance test (OGTT) for the reassessment of the carbohydrate metabolism status in postpartum women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We evaluated the status of carbohydrate metabolism by performing the OGTT and fasting glucose and A1C tests in 231 postpartum women with prior GDM 1 year after delivery. RESULTS The prevalence of abnormal carbohydrate metabolism was 45.89% by the OGTT criterion, 19.05% by the A1C test criterion, 38.10% by the fasting glucose test criterion, and 46.75% by the A1C-fasting glucose test criteria. Using the OGTT as the gold standard, abnormal carbohydrate metabolism according to the A1C test criterion had 22.64% sensitivity and 54.55% positive predictive value; abnormal carbohydrate metabolism by the fasting glucose criterion had 83.02% sensitivity and 100% positive predictive value. The A1C-fasting glucose test criteria classified 18 women with normal carbohydrate metabolism as having abnormal carbohydrate metabolism. Abnormal carbohydrate metabolism by the A1C-fasting glucose test criteria had 83.02% sensitivity and 81.48% positive predictive value. CONCLUSIONS Our results seem to indicate that the A1C test criterion alone or in combination with fasting glucose test criterion does not provide a sensitive and specific diagnosis of abnormal carbohydrate metabolism in women who have had GDM.

Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients

The low-grade inflammation observed in obesity has been associated with a high-fat diet, though this relation is not fully understood. Bacterial endotoxin, produced by gut microbiota, may be the linking factor. However, this has not been confirmed in obese patients. To study the relationship between a high-fat diet and bacterial endotoxin, we analyzed postprandial endotoxemia in morbidly obese patients after a fat overload. The endotoxin levels were determined in serum and the chylomicron fraction at baseline and 3 h after a fat overload in 40 morbidly obese patients and their levels related with the degree of insulin resistance and postprandial hypertriglyceridemia. The morbidly obese patients with the highest postprandial hypertriglyceridemia showed a significant increase in lipopolysaccharide (LPS) levels in serum and the chylomicron fraction after the fat overload. Postprandial chylomicron LPS levels correlated positively with the difference between postprandial triglycerides and baseline triglycerides. There were no significant correlations between C-reactive protein (CRP) and LPS levels. The main variables contributing to serum LPS levels after fat overload were baseline and postprandial triglyceride levels but not glucose or insulin resistance. Additionally, superoxide dismutase activity decreased significantly after the fat overload. Postprandial LPS increase after a fat overload is related to postprandial hypertriglyceridemia but not to degree of insulin resistance in morbidly obese patients.

Comparative study of microbial-derived phenolic metabolites in human feces after intake of gin, red wine, and dealcoholized red wine.

The analysis of microbial phenolic metabolites in fecal samples from in vivo studies is crucial to understanding the potential modulatory effects derived from polyphenol consumption and its overall health effects, particularly at the gut level. In this study, the composition of microbial phenolic metabolites in human feces collected after regular consumption of either red wine, dealcoholized red wine, or gin was analyzed by UPLC-ESI-MS/MS. Red wine interventions produce a change in the content of eight phenolic acids, which are probably derived from the catabolism of flavan-3-ols and anthocyanins, the main flavonoids in red wine. Moreover, alcohol seemed not to influence the formation of phenolic metabolites by the gut microbiota. A principal component analysis revealed large interindividual differences in the formation of microbial metabolites after each red wine polyphenol intervention, but not after the gin intervention, indicating differences in the gut microbial composition among subjects.

PPARγ Expression After a High-fat Meal Is Associated With Plasma Superoxide Dismutase Activity in Morbidly Obese Persons

Peroxisome proliferator‐activated receptor‐γ (PPARγ) may play a protective role in the regulation of vascular function, partly mediated by its effects on superoxide dismutase (SOD). The aim of this study was to determine the association between PPARγ expression in peripheral blood mononuclear cells (PBMCs) and SOD activity in morbidly obese persons with varying degrees of insulin resistance (IR). We studied in 10 morbidly obese persons (five with no IR and five with high IR) the effect of a high‐fat meal on the plasma activity of various antioxidant enzymes and the mRNA expression of PPARγ in PBMC. The high‐fat meal resulted in a significant decrease in plasma SOD activity, glutathione reductase (GSH‐Rd) activity, and mRNA expression of PPARγ only in the group of morbidly obese persons with high IR. PPARγ expression after the high‐fat meal correlated with the IR levels (r = −0.803, P = 0.009) and the plasma SOD activity (r = 0.903, P = 0.001). Likewise, the reduction in PPARγ expression correlated with the increase in free fatty acids (FFA) (r = 0.733, P = 0.016). In conclusion, the decreased expression of PPARγ in PBMC in morbidly obese persons after a high‐fat meal was associated with the state of IR, the plasma SOD activity, and the changes in the concentration of FFA.

Oxidative stress and metabolic changes after continuous positive airway pressure treatment according to previous metabolic disorders in sleep apnea-hypopnea syndrome patients

Sleep apnea-hypopnea syndrome (SAHS) is characterized by recurrent episodes of hypoxia/reoxygenation, which seems to promote oxidative stress. SAHS patients experience increases in hypertension, obesity, and dyslipidemia, and the oxidative state has been related to the genesis of these disorders. The purpose of this study was to examine the changes in oxidative stress markers and metabolic parameters in S AHS patients after 1 month of treatment with continuous positive airway pressure (CPAP), in relation to their previous metabolic disorders. The study included 78 SAHS patients who required CPAP. The patients were classified according to their disorders, including hypertension, obesity, and dyslipidemia. Measurements were made before and after 1 month of treatment with CPAP. The diastolic blood pressure decreased after treatment in all the patients, significantly so in those who were nondyslipidemic, obese, or hypertensive (the systolic pressure also fell in these latter patients). Plasma oxidative stress biomarkers showed a significant antioxidant capacity and increased activity (P<0.05) after treatment, more so in the nondyslipidemic and hypertensive patients. Furthermore, serum lipid peroxidation levels decreased after CPAP (P<0.01). No change was observed in insulin resistance (IR) after CPAP treatment in any of the different disorders. In conclusion, oxidative stress markers improved significantly after CPAP treatment in SAHS patients, especially in the nondyslipidemic and hypertensive patients. Moreover, the blood pressure decreased after CPAP treatment, particularly in the obese, nondyslipidemic, and hypertensive patients. No significant change in IR was found in any of the SAHS patients after CPAP treatment.

Caspase Induction and BCL2 Inhibition in Human Adipose Tissue: A potential relationship with insulin signaling alteration

OBJECTIVE Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants. CONCLUSIONS Body fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance.

GLP‐1 and peptide YY secretory response after fat load is impaired by insulin resistance, impaired fasting glucose and type 2 diabetes in morbidly obese subjects

Both glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) are gut hormones involved in energy homoeostasis. Obesity, insulin resistance and hyperglycaemia are significant confounders when GLP‐1 and PYY secretion is assessed. Thus, we evaluated GLP‐1 and PYY response after fat load in morbidly obese patients with different degrees of insulin resistance and glycemic status.