Explore the vast range of titles available.

ObjectiveThe gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin.DesignThe stools from four obese donors differing by microbial diversity and composition were sampled before the dietary intervention and inoculated to antibiotic-pretreated mice (hum-ob mice; humanised obese mice). Hum-ob mice were fed with a high-fat diet and treated with inulin. Metabolic and microbiota changes on inulin treatment in hum-ob mice were compared with those obtained in a cohort of obese individuals supplemented with inulin for 3 months.ResultsWe show that hum-ob mice colonised with the faecal microbiota from different obese individuals differentially respond to inulin supplementation on a high-fat diet. Among several bacterial genera, Barnesiella, Bilophila, Butyricimonas, Victivallis, Clostridium XIVa, Akkermansia, Raoultella and Blautia correlated with the observed metabolic outcomes (decrease in adiposity and hepatic steatosis) in hum-ob mice. In addition, in obese individuals, the preintervention levels of Anaerostipes, Akkermansia and Butyricicoccus drive the decrease of body mass index in response to inulin.ConclusionThese findings support that characterising the gut microbiota prior to nutritional intervention with prebiotics is important to increase the positive outcome in the context of obesity and metabolic disorders.

ObjectiveTo investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction.DesignWe examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe−/−) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed.ResultsITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe−/− mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation.ConclusionsWe demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.

The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis) in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L) in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay). These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle.

A saffron extract has been found to be effective in the context of depression and anxiety, but its effect on sleep quality has not been investigating yet using objective approaches. For this purpose, a randomized double-blind controlled study was conducted in subjects presenting mild to moderate sleep disorder associated with anxiety. Sixty-six subjects were randomized and supplemented with a placebo (maltodextrin) or a saffron extract (15.5 mg per day) for 6 weeks. Actigraphy was used to collect objective data related to sleep quality at baseline, at the middle and at the end of the intervention. Sleep quality was also assessed by completion of the LSEQ and PSQI questionnaires and quality of life by completion of the SF-36 questionnaire. Six weeks of saffron supplementation led to an increased time in bed assessed by actigraphy, to an improved ease of getting to sleep evaluated by the LSEQ questionnaire and to an improved sleep quality, sleep latency, sleep duration, and global scores evaluated by the PSQI questionnaire, whereas those parameters were not modified by the placebo. In conclusion, those results suggest that a saffron extract could be a natural and safe nutritional strategy to improve sleep duration and quality.

Conjugated linoleic acids are linoleic acid isomers found in the diet that can also be produced through bacterial metabolism of polyunsaturated fatty acids. Our objective was to evaluate the contribution of fatty acid metabolites produced from polyunsaturated fatty acids by the gut microbiota in vivo to regulation of hepatic lipid metabolism and steatosis. In mice with depleted n-3 polyunsaturated fatty acids, we observed an accumulation of trans-11,trans-13 CLA and cis-9,cis-11 conjugated linoleic acids in the liver tissue that were associated with an increased triglyceride content and expression of lipogenic genes. We used an in vitro model to evaluate the impact of these two conjugated linoleic acids on hepatic lipid metabolism. In HepG2 cells, we observed that only trans-11,trans-13 conjugated linoleic acids recapitulated triglyceride accumulation and increased lipogenic gene expression, which is a phenomenon that may implicate the nuclear factors sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP). The trans-11,trans-13 conjugated linoleic acids can stimulate hepatic lipogenesis, which supports the conclusion that gut microbiota and related metabolites should be considered in the treatment of non-alcoholic liver disease.

Patients with non-alcoholic fatty liver disease are characterised by a decreased n-3/n-6 polyunsaturated fatty acid (PUFA) ratio in hepatic phospholipids. The metabolic consequences of n-3 PUFA depletion in the liver are poorly understood. We have reproduced a drastic drop in n-3 PUFA among hepatic phospholipids by feeding C57Bl/6J mice for 3 months with an n-3 PUFA depleted diet (DEF) versus a control diet (CT), which only differed in the PUFA content. DEF mice exhibited hepatic insulin resistance (assessed by euglycemic-hyperinsulinemic clamp) and steatosis that was associated with a decrease in fatty acid oxidation and occurred despite a higher capacity for triglyceride secretion. Microarray and qPCR analysis of the liver tissue revealed higher expression of all the enzymes involved in lipogenesis in DEF mice compared to CT mice, as well as increased expression and activation of sterol regulatory element binding protein-1c (SREBP-1c). Our data suggest that the activation of the liver X receptor pathway is involved in the overexpression of SREBP-1c, and this phenomenon cannot be attributed to insulin or to endoplasmic reticulum stress responses. In conclusion, n-3 PUFA depletion in liver phospholipids leads to activation of SREBP-1c and lipogenesis, which contributes to hepatic steatosis.

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 (Apoc3, inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.

Inulin-type fructans (ITF) are known for their capacity to modulate gut microbiota, energy metabolism and to improve glycemia in several animal models of obesity, and in humans. The potential contribution of ITF as modulators of sugar digestion by host enzymes has not been evaluated yet. A sucrose challenge has been performed on naive mice fed a standard diet supplemented with or without native chicory inulin (Fibruline 5%) for 3 weeks. The area under the curve of glycemia as well as sucrase activity in the small intestine were lowered after inulin treatment. Pyrosequencing of the 16S rRNA gene confirmed important changes in gut microbiota (mostly in favor of Blautia genus) due to inulin extract supplementation. Interestingly, the suppressive effect of inulin extract on postprandial glycemia also occurred when inulin was directly added to the sucrose solution, suggesting that the effect on sucrose digestion did not require chronic inulin administration. In vitro tests confirmed a direct inhibition of sucrase enzyme by the inulin extract, thereby suggesting that native chicory inulin, in addition to its well-known prebiotic effect, is also able to decrease the digestibility of carbohydrates, a phenomenon that can contribute in the control of post prandial glycemia. We may not exclude that the sucrose escaping the digestion could also contribute to the changes in the gut microbiota after a chronic treatment with inulin.

Backround Western diet is characterized by an insufficient n-3 polyunsaturated fatty acid (PUFA) consumption which is known to promote the pathogenesis of several diseases. We have previously observed that mice fed with a diet poor in n-3 PUFA for two generations exhibit hepatic steatosis together with a decrease in body weight. The gut microbiota contributes to the regulation of host energy metabolism, due to symbiotic relationship with fermentable nutrients provided in the diet. In this study, we have tested the hypothesis that perturbations of the gut microbiota contribute to the metabolic alterations occurring in mice fed a diet poor in n-3 PUFA for two generations (n-3/- mice). Methods C57Bl/6J mice fed with a control or an n-3 PUFA depleted diet for two generations were supplemented with prebiotic (inulin-type Fructooligosaccharides, FOS, 0.20 g/day/mice) during 24 days. Results n-3/-mice exhibited a marked drop in caecum weight, a decrease in lactobacilli and an increase in bifidobacteria in the caecal content as compared to control mice (n-3/+ mice). Dietary supplementation with FOS for 24 days was sufficient to increase caecal weight and bifidobacteria count in both n-3/+ and n-3/-mice. Moreover, FOS increased lactobacilli content in n-3/-mice, whereas it decreased their level in n-3/+ mice. Interestingly, FOS treatment promoted body weight gain in n-3/-mice by increasing energy efficiency. In addition, FOS treatment decreased fasting glycemia and lowered the higher expression of key factors involved in the fatty acid catabolism observed in the liver of n-3/-mice, without lessening steatosis. Conclusions the changes in the gut microbiota composition induced by FOS are different depending on the type of diet. We show that FOS may promote lactobacilli and counteract the catabolic status induced by n-3 PUFA depletion in mice, thereby contributing to restore efficient fat storage.

Malnutrition is a highly prevalent condition in older adults. It is associated with low muscle mass and function and increased occurrence of health problems. Maintaining an adequate nutritional status as well as a sufficient nutrient intake in older people is therefore essential to address this public health problem. For this purpose, protein supplementation is known to prevent the loss of muscle mass during aging, and the consumption of various pomegranate extracts induces numerous health benefits, mainly through their antioxidant properties. However, to our knowledge, no study has to date investigated the impact of their combination on the level of malnutrition in older people. The objective of this preliminary study was thus to evaluate the safety of a combination of protein and a pomegranate extract in healthy subjects aged 65 years or more during a 21-day supplementation period. Thirty older participants were randomly assigned to receive protein and a pomegranate extract (Test group) or protein and maltodextrin (Control group) during a 21-day intervention period. The primary outcomes were the safety and tolerability of the supplementation defined as the occurrence of adverse events, and additional secondary outcomes included physical examination and hematological and biochemical parameters. No serious adverse events were reported in any group. Changes in physical, hematological, and biochemical parameters between the initial screening and the end of the study were equivalent in both groups, except for glutamate-pyruvate transaminase (GPT) and prealbumin, for which a decrease was observed only in the Test group. Our initial findings support the safety of the combination of protein and a pomegranate extract in healthy elderly people. Future clinical trials on a larger sample and a longer period are needed to determine the efficacy of this combination.