Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism

OBJECTIVE: To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. DESIGN: To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH). RESULTS: Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. CONCLUSIONS: Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans

Prebiotic Effects of Wheat Arabinoxylan Related to the Increase in Bifidobacteria, Roseburia and Bacteroides/Prevotella in Diet-Induced Obese Mice

BACKGROUND: Alterations in the composition of gut microbiota--known as dysbiosis--has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters. CONCLUSIONS/SIGNIFICANCE: Supplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti-inflammatory and anti-obesity effects are related to changes in gut microbiota. These data support a role for wheat AX as interesting nutrients with prebiotic properties related to obesity prevention

Production of PUFA-derived metabolites by the gut microbiota

More and more evidence show that the trillions of bacteria housed in the gastro-intestinal tract, and called the gut microbiota, are able to influence host physiology, namely by producing bioactive metabolites prone to regulate host metabolism. Due to the very high metabolic potential of the gut microbiota, a near infinite metabolic potential could be envisaged, in addition to the well known short-chain fatty acids, bile acids, or choline-derivatives. In this doctoral thesis, we proposed that polyunsaturated fatty acid (PUFA)-derived metabolites could be a new kind of bioactive metabolites produced by the gut microbiota. This hypothesis is supported by in vitro studies performed with isolated gut bacteria, mainly Bifidobacterium spp., Lactobacillus spp. and Roseburia spp., which are able to produce CLA (conjugated linoleic acid) and CLnA (conjugated linolenic acid) or other non-conjugated metabolites such as vaccenic acid. Our experimental work provides evidence that the gut microbiota is able to produce, in vivo, PUFA-derived metabolites. Modulations of the gut microbiota composition, by high-fat diet feeding or prebiotic supplementations, change its ability to produce these metabolites. Furthermore, we highlight that both the type and the quantity of substrate (PUFA) available in the gut for bacterial metabolism also influence the profile of PUFA-derived metabolites produced by the gut microbiota. Furthermore, we show that the main production site of these metabolites is the distal part of the gut (i.e. the caecum and colon). Even if PUFA-derived metabolites are accumulating in intestinal tissues, our studies reveal that their systemic availability remains limited, suggesting that their relevance in host metabolism regulation would be of most importance at the intestinal level. In complement of the experimental work performed on mice models, we have the opportunity to use human samples obtained during a prebiotic-intervention on obese individuals. No major modifications of the fatty acid profile, including PUFA-derived metabolites, were observed between the beginning and the end of both treatments (prebiotic and placebo) and between placebo-treated and prebiotic-treated patients. However, we highlighted interesting correlations between specific CLA and CLnA and some bacteria (for example Bifidobacterium spp. and Lactobacillus spp.) known to be able to produce these metabolites in vitro from fatty acid, supporting the production of PUFA-derived metabolites by the gut microbiota in human. Our experimental data underline the importance to further pay attention to unknown metabolites produced by the gut microbes, when evaluating host-gut microbiota interactions in human health.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201

Analytical monitoring of the chemicals present in the discharge water generated by the surface treatment industry

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Use of pasteurized Akkermansia for treating metabolic disorders

The present invention relates to pasteurized Akkermansia muciniphila or fragments thereof for treating a metabolic disorder in a subject in need thereof. The present invention also relates to a composition, a pharmaceutical composition and a medicament comprising pasteurized Akkermansia muciniphila or fragments thereof for treating a metabolic disorder. The present invention also relates to the use of pasteurized Akkermansia muciniphila or fragments thereof for promoting weight loss in a subject in need thereof

Chapitre III. Campagne RSDE – Recherche et réduction des substances dangereuses dans l’eau

1. Introduction Parmi les sources potentielles de pollution, le secteur industriel, a entrepris depuis de nombreuses années, des efforts importants afin de réduire et de surveiller les volumes de polluants rejetés dans le milieu aquatique (Eckenfelder, 2001 ; Cox et al., 2006 ; Crini et Badot, 2007). En effet, à partir des années 1970, des investissements ont été, par exemple, réalisés pour mettre en œuvre des technologies de traitement des eaux usées via l’installation sur site de stations d..

Role of the lower and upper intestine in the production and absorption of gut microbiota-derived PUFA metabolites.

In vitro studies have suggested that isolated gut bacteria are able to metabolize PUFA into CLA (conjugated linoleic acids) and CLnA (conjugated linolenic acids). However, the bioavailability of fatty acid metabolites produced in vivo by the gut microbes remains to be studied. Therefore, we measured intestinal concentration and plasma accumulation of bacterial metabolites produced from dietary PUFA in mice, first injected with a lipoprotein lipase inhibitor, then force-fed with either sunflower oil (200 µl) rich in n-6 PUFA or linseed oil (200 µl) rich in n-3 PUFA. The greatest production of bacterial metabolites was observed in the caecum and colon, and at a much lesser extent in the jejunum and ileum. In the caecal content, CLA proportions were higher in sunflower oil force-fed mice whereas CLnA proportions were higher in linseed oil force-fed mice. The accumulation of the main metabolites (CLA cis-9,trans-11-18:2 and CLnA cis-9,trans-11,cis-15-18:3) in the caecal tissue was not associated with their increase in the plasma, therefore suggesting that, if endogenously produced CLA and CLnA have any biological role in host metabolism regulation, their effect would be confined at the intestinal level, where the microbiota is abundant

Gut–Kidney Axis Investigations in Animal Models of Chronic Kidney Disease

International audienceChronic kidney disease (CKD) is an incurable disease in which renal function gradually declines, resulting in no noticeable symptoms during the early stages and a life-threatening disorder in the latest stage. The changes that accompany renal failure are likely to influence the gut microbiota, or the ecosystem of micro-organisms resident in the intestine. Altered gut microbiota can display metabolic changes and become harmful to the host. To study the gut–kidney axis in vivo, animal models should ideally reproduce the disorders affecting both the host and the gut microbiota. Murine models of CKD, but not dog, manifest slowed gut transit, similarly to patient. Animal models of CKD also reproduce altered intestinal barrier function, as well as the resulting leaky gut syndrome and bacterial translocation. CKD animal models replicate metabolic but not compositional changes in the gut microbiota. Researchers investigating the gut–kidney axis should pay attention to the selection of the animal model (disease induction method, species) and the setting of the experimental design (control group, sterilization method, individually ventilated cages) that have been shown to influence gut microbiota

First report in a river in France of the benthic cyanobacterium Phormidium favosum producing anatoxin-a associated with dog neurotoxicosis

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