Search

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investigate (a) whether GDF-15 concentrations were associated with liver fibrosis and involved in the relationship between T2DM and liver fibrosis and (b) what factors linked with T2DM are associated with increased GDF-15 concentrations. METHODS: Ninety-nine patients with NAFLD (61% men, 42.4% T2DM) were studied. Serum GDF-15 concentrations were measured by electro-chemiluminescence immunoassay. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. Regression modelling, receiver operator characteristic curve analysis and Sobel test statistics were used to test associations, risk predictors and the involvement of GDF-15 in the relationship between T2DM and liver fibrosis, respectively. RESULTS: Patients with NAFLD and T2DM (n = 42) had higher serum GDF-15 concentrations [mean (SD): 1271.0 (902.1) vs. 640.3 (332.5) pg/ml, p < 0.0001], and a higher proportion had VCTE assessed ≥F2 fibrosis (48.8 vs. 23.2%, p = 0.01) than those without T2DM. GDF-15 was independently associated with liver fibrosis (p = 0.001), and GDF-15 was the most important single factor predicting ≥F2 or ≥F3 fibrosis (≥F2 fibrosis AUROC 0.75, (95% CI 0.63-0.86), p < 0.001, with sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values of 56.3%, 86.9%, 69.2% and 79.1%, respectively). GDF-15 was involved in the association between T2DM and ≥F2 fibrosis (Sobel test statistic 2.90, p = 0.004). Other factors associated with T2DM explained 60% of the variance in GDF-15 concentrations (p < 0.0001). HbA1c concentrations alone explained 30% of the variance (p < 0.0001). CONCLUSIONS: GDF-15 concentr

Knowing how dietary fibre nourishes gut microorganisms might suggest ways to boost health-promoting bacteria. A method developed to pinpoint bacteria that consume particular types of dietary fibre could advance such efforts.

BACKGROUND : Undernutrition predisposes children to a greater incidence and duration of diarrhea. No review and meta-analysis have yet been conducted to assess effectiveness of probiotics and synbiotics in undernourished children. AIMS : To assess the effectiveness of probiotics and synbiotics on diarrhea in undernourished children. METHODS : Randomized, double-blind, placebo-controlled trials evaluating the effects of probiotics and synbiotics on diarrhea in undernourished children were searched from 1990 to May 2020. Recommendations of the Cochrane Handbook and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement were followed. RESULTS : The systematic review identified 15 trials with 6986 patients. The meta-analysis revealed that treatment with probiotic or synbiotic reduced significantly both the duration of diarrhea [Weighted mean difference (WMD) = −1.05 day, 95% CI (−1.98, −0.11)] and the hospital stay duration [Standard mean difference (SMD) = −2.87 days, 95% CI (−5.33, −0.42)], especially in specific patient subsets. In both groups, similar rates of vomiting and nutritional recovery were observed. No probiotics or synbiotics-related adverse effects were reported. Subgroup analyses showed that probiotic and synbiotic treatment were more effective in reducing risk of diarrhea in outpatients [Risk ratio (RR) = 0.86, 95%CI (0.75–0.98)]. CONCLUSION : This meta-analysis supports the potential beneficial roles of probiotics and synbiotics on diarrhea in undernourished children.

Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic complications. To date, the majority of the research on cachexia has been focused on skeletal muscle, muscle atrophy being a pivotal cause of weight loss and the major feature associated with the steep reduction in quality of life. Nevertheless, defining the impact of cachexia on other organs is essential to properly comprehend the complexity of such a condition and potentially develop novel therapeutic approaches.

Le cancer de l’œsophage est un cancer particulièrement agressif, avec 450 000 nouveaux cas par an dans le monde. Malgré les récentes innovations thérapeutiques en oncologie, la radiochimiothérapie reste le traitement standard dans ce cancer. Ce traitement lourd est pourtant peu efficace, puisque la survie des patients 5 ans après le diagnostic atteint seulement 20%. Une meilleure connaissance des mécanismes moléculaires ainsi que de nouveaux marqueurs pronostics sont nécessaires afin de réaliser une avancée significative dans la compréhension du cancer de l’œsophage. L’objectif de ce travail concerne l’investigation de nouveaux paramètres pronostiques, macro- ou microenvironnementaux.Dans ce cadre, nous avons investigué l’impact de la composition corporelle et, plus particulièrement, de la qualité du tissu adipeux des patients sur leur survie générale. Les patients souffrant d’un cancer de l’œsophage présentent en général un statut nutritionnel complexe :l’obésité est un facteur de risque de développement d’un adénocarcinome de l’œsophage, tandis que les carcinomes épidermoïdes se développent fréquemment chez des patients malnutris. Nous avons montré que l’atténuation du tissu graisseux au CT-scan a un impact pronostique important. Spécifiquement, une faible densité de la graisse sous-cutanée et viscérale sont des facteurs pronostiques bénéfiques majeurs. Des résultats similaires ont été publiés pour d’autres cancers digestifs, notamment par notre équipe pour le cancer colorectal métastatique. Cependant, les mécanismes biologiques sous-tendant les variations de densité de ces tissus graisseux restent encore incertains. Un tissu graisseux de haute densité refléterait des adipocytes beiges, pauvres en triglycérides et métaboliquement plus actifs. Alors que des phénomènes extrinsèques à la tumeur pourraient amorcer ce phénomène, les facteurs sécrétés par la tumeur pourraient empirer ce processus et impacter l’état de santé général du patient. Nos résultats suggèrent qu, Doctorat en Sciences biomédicales et pharmaceutiques (Médecine), info:eu-repo/semantics/nonPublished

AU-rich element (ARE)-mediated mRNA decay represents a key mechanism to avoid excessive production of inflammatory cytokines. Tristetraprolin (TTP, encoded by Zfp36) is a major ARE-binding protein, since Zfp36−/− mice develop a complex multiorgan inflammatory syndrome that shares many features with spondyloarthritis. The role of TTP in intestinal homeostasis is not known. Herein, we show that Zfp36−/− mice do not develop any histological signs of gut pathology. However, they display a clear increase in intestinal inflammatory markers and discrete alterations in microbiota composition. Importantly, oral antibiotic treatment reduced both local and systemic joint and skin inflammation. We further show that absence of overt intestinal pathology is associated with local expansion of regulatory T cells. We demonstrate that this is related to increased vitamin A metabolism by gut dendritic cells, and identify RALDH2 as a direct target of TTP. In conclusion, these data bring insights into the interplay between microbiota-dependent gut and systemic inflammation during immune-mediated disorders, such as spondyloarthritis., SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPE: Enhanced adiposity and metabolic inflammation are major features of obesity associated with altered gut microbiota and intestinal barrier. How these metabolic outcomes can be impacted by milk polar lipids (MPL), naturally containing 25% of sphingomyelin, is investigated in mice fed a mixed high-fat (HF) diet . METHODS AND RESULTS: Male C57Bl/6 mice receive a HF-diet devoid of MPL (21% fat, mainly palm oil, in chow), or supplemented with 1.1% or 1.6% of MPL (HF-MPL1; HF-MPL2) via a total-lipid extract from butterserum concentrate for 8 weeks. HF-MPL2 mice gain less weight versus HF (p < 0.01). Diets do not impact plasma markers of inflammation but in the liver, HF-MPL2 tends to decrease hepatic gene expression of macrophage marker F4/80 versus HF-MPL1 (p = 0.06). Colonic crypt depth is the maximum in HF-MPL2 (p < 0.05). In cecal microbiota, HF-MPL1 increases Bifidobacterium animalis versus HF (p < 0.05). HF-MPL2 decreases Lactobacillus reuteri (p < 0.05), which correlates negatively with the fecal loss of milk sphingomyelin-specific fatty acids (p < 0.05). CONCLUSION: In mice fed a mixed HF diet, MPL can limit HF-induced body weight gain and modulate gut physiology and the abundance in microbiota of bacteria of metabolic interest. This supports further exploration of how residual unabsorbed lipids reaching the colon can impact HF-induced metabolic disorders.

This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut-liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.

Obesity has been recognized by the World Health Organization as a global epidemic. The gut microbiota is considered as a factor involved in the regulation of numerous metabolic pathways by impacting several functions of the host. It has been suggested that probiotics can modulate host gene expression and metabolism, and thereby positively influence host adipose tissue development and obesity related-metabolic disorders. The aim of the present work was to evaluate the effect of an exopolysaccharide (EPS)-producing Bifidobacterium strain on host glucose and lipid metabolism and the gut microbial composition in a short-term diet-induced obesity (DIO) in mice. C57BL/6J male mice were randomly divided into three groups: a control group that received control standard diet, a group fed a high-fat diet (HF), and a group fed HF supplemented with Bifidobacterium animalis IPLA R1. Fasting serum insulin as well as triglycerides accumulation in the liver were significantly reduced in the group receiving B. animalis IPLA R1. The treatment with the EPS-producing B. animalis IPLA R1 tended to down-regulate the expression of host genes involved in the hepatic synthesis of fatty acids which was concomitant with an upregulation in the expression of genes related with fatty acid oxidation. B. animalis IPLA R1 not only promoted the increase of Bifidobacterium but also the levels of Bacteroides-Prevotella. Our data indicate that the EPS-producing Bifidobacterium IPLA R1 strain may have beneficial effects in metabolic disorders associated with obesity, by modulating the gut microbiota composition and promoting changes in lipids metabolism and glucose homeostasis.

The prevalence of osteoarthritis (OA) increases not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and diets low in fiber and rich in sugar and saturated fats, which promote chronic low-grade inflammation and obesity. Adverse alterations of the gut microbiota (GMB) composition, called microbial dysbiosis, may favor metabolic syndrome and inflammaging, two important components of OA onset and evolution. Considering the burden of OA and the need to define preventive and therapeutic interventions targeting the modifiable components of OA, an expert working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) to review the potential contribution of GMB to OA. Such a contribution is supported by observational or dietary intervention studies in animal models of OA and in humans. In addition, several well-recognized risk factors of OA interact with GMB. Lastly, GMB is a critical determinant of drug metabolism and bioavailability and may influence the response to OA medications. Further research targeting GMB or its metabolites is needed to move the field of OA from symptomatic management to individualized interventions targeting its pathogenesis.

Cachexia occurs in many chronic diseases and is associated with increased morbidity and mortality. It is treated by nutritional support but often with limited effectiveness, leading to the search of other therapeutic strategies. The modulation of gut microbiota, whether through pro-, pre-, syn- or antibiotics or fecal transplantation, is attracting ever-growing interest in the field of obesity, but could also be an interesting and innovative alternative for treating cachexia. This article reviews the evidence linking the features of malnutrition, as defined by the Global Leadership Initiative on Malnutrition [low body mass index (BMI), unintentional body weight loss, low muscle mass, low appetite, and systemic inflammation] and the gut microbiota in human adults with cachexia-associated diseases, and shows the limitations of the present research in that field with suggestions for future directions.

The vascular dysfunction is the primary event in the occurrence of cardio-vascular risk, and no treatment exists until now. We tested for the first time the hypothesis that chitin-glucan (CG) - an insoluble fibre with prebiotic properties- and polyphenol-rich pomegranate peel extract (PPE) can improve endothelial and inflammatory disorders in a mouse model of cardiovascular disease (CVD), namely by modulating the gut microbiota. Male Apolipoprotein E knock-out (ApoE-/-) mice fed a high fat (HF) diet developed a significant endothelial dysfunction attested by atherosclerotic plaques and increasing abundance of caveolin-1 in aorta. The supplementation with CG + PPE in the HF diet reduced inflammatory markers both in the liver and in the visceral adipose tissue together with a reduction of hepatic triglycerides. In addition, it increased the activating form of endothelial NO-synthase in mesenteric arteries and the heme-nitrosylated haemoglobin (Hb-NO) blood levels as compared with HF fed ApoE-/- mice, suggesting a higher capacity of mesenteric arteries to produce nitric oxide (NO). This study allows to pinpoint gut bacteria, namely Lactobacillus and Alistipes, that could be implicated in the management of endothelial and inflammatory dysfunctions associated with CVD, and to unravel the role of nutrition in the modulation of those bacteria.

SCOPE: Cereals are important sources of carbohydrates, but also contain nutrients that could impact adiposity. The contribution of gluten to obesity and the effects of prebiotics-arabinoxylo-oligosaccharides (AXOS) and fructo-oligosaccharides (FOS)-that can be extracted from gluten-containing cereals are analyzed. METHODS AND RESULTS: Mice are fed a control diet, Western diet (WD, consisting of high fat/high sucrose), or WD with 5% gluten. Prebiotics are tested in the WD with gluten. Gluten does not increase body weight and has a minor effect on ileal inflammation. Gluten decreases the expression of browning markers in the fat and increases the triglycerides synthesis in the muscle. AXOS decreases body weight and adiposity in fat pads muscle and liver. AXOS promotes gluten cleavage by the induction of prolyl endopeptidase that is translated into a reduction of gluten immunogenic peptides. Gluten has minor effects on cecal microbiota composition, whereas prebiotics increased Bifidobacterium, Butyricicoccus, Prevotella, and Parasutterella, which are all negatively correlated to the cecal content of gluten peptides. CONCLUSION: While gluten may affect metabolic homeostasis, these effects are lessened when gluten is consumed along with cereal-derived fibers. If confirmed in humans, the authors bring new arguments to eat fiber-rich cereals to promote a healthy diet.

Orosensory perception of sweet stimulus is blunted in diet-induced obese (DIO) rodents. Although this alteration might contribute to unhealthy food choices, its origin remains to be understood. Cumulative evidence indicates that prebiotic manipulations of the gut microbiota are associated with changes in food intake by modulating hedonic and motivational drive for food reward. In the present study, we explore whether a prebiotic supplementation can also restore the taste sensation in DIO mice. The preference and licking behavior in response to various sucrose concentrations were determined using respectively two-bottle choice tests and gustometer analysis in lean and obese mice supplemented or not with 10% inulin-type fructans prebiotic (P) in a preventive manner. In DIO mice, P addition reduced the fat mass gain and energy intake, limited the gut dysbiosis and partially improved the sweet taste perception (rise both of sucrose preference and number of licks/10 s vs. non-supplemented DIO mice). No clear effect on orosensory perception of sucrose was found in the supplemented control mice. Therefore, a preventive P supplementation can partially correct the loss of sweet taste sensitivity found in DIO mice, with the efficiency of treatment being dependent from the nutritional status of mice (high fat diet vs. regular chow).

BACKGROUND : Inulin-type fructans (ITFs) are a type of fermentable dietary fiber that can confer beneficial health effects through changes in the gut microbiota. However, their effect on gut sensitivity and nutritional behavior is a matter of debate. OBJECTIVE : We evaluated the impact of consuming ITF-rich vegetables daily on gut microbiota, gastro-intestinal symptoms, and food-related behavior in healthy individuals. METHODS : A single group-design trial was conducted in 26 healthy individuals. During 2 wk, the participants were instructed to adhere to a controlled diet based on ITF-rich vegetables (providing a mean intake of 15 g ITF/d). Three test days were organized: before and after the nutritional intervention and 3 wk after returning to their usual diet. We assessed nutrient intake, food-related behavior, fecal microbiota composition, microbial fermentation, and gastrointestinal symptoms. RESULTS : The major microbial modifications during the intervention were an increased proportion of the Bifidobacterium genus, a decreased level of unclassified Clostridiales, and a tendency to decrease Oxalobacteraceae. These changes were reversed 3 wk after the intervention. The volunteers showed greater satiety, a reduced desire to eat sweet, salty, and fatty food, and a trend to increase hedonic attitudes towards some inulin-rich vegetables. Only flatulence episodes were reported during the dietary intervention, whereas intestinal discomfort, inversely associated with Clostridium cluster IV and Ruminococcus callidus, was improved at the end of the intervention. CONCLUSIONS : A higher consumption of ITF-rich vegetables allows a substantial increase in well-tolerated dietary fiber, which may in turn improve food-related behavior. Moreover, it leads to beneficial modifications of the gut microbiota composition and function. This trial is registered at clinicaltrial.gov as NCT03540550.

Obesity has been recognized by the World Health Organization as a global epidemic. The gut microbiota is considered as a factor involved in the regulation of numerous metabolic pathways by impacting several functions of the host. It has been suggested that probiotics can modulate host gene expression and metabolism, and thereby positively influence host adipose tissue development and obesity related-metabolic disorders. The aim of the present work was to evaluate the effect of an exopolysaccharide (EPS)-producing Bifidobacterium strain on host glucose and lipid metabolism and the gut microbial composition in a short-term diet-induced obesity (DIO) in mice. C57BL/6J male mice were randomly divided into three groups: a control group that received control standard diet, a group fed a high-fat diet (HF), and a group fed HF supplemented with Bifidobacterium animalis IPLA R1. Fasting serum insulin as well as triglycerides accumulation in the liver were significantly reduced in the group receiving B. animalis IPLA R1. The treatment with the EPS-producing B. animalis IPLA R1 tended to down-regulate the expression of host genes involved in the hepatic synthesis of fatty acids which was concomitant with an upregulation in the expression of genes related with fatty acid oxidation. B. animalis IPLA R1 not only promoted the increase of Bifidobacterium but also the levels of Bacteroides-Prevotella. Our data indicate that the EPS-producing Bifidobacterium IPLA R1 strain may have beneficial effects in metabolic disorders associated with obesity, by modulating the gut microbiota composition and promoting changes in lipids metabolism and glucose homeostasis.