Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice

Recent evidence indicates that the gut microbiota plays a key role in the pathophysiology of obesity. Indeed, diet-induced obesity (DIO) has been associated to substantial changes in gut microbiota composition in rodent models. In the context of obesity, enhanced adiposity is accompanied by low-grade inflammation of this tissue but the exact link with gut microbial community remains unknown. In this report, we studied the consequences of high-fat diet (HFD) administration on metabolic parameters and gut microbiota composition over different periods of time. We found that Akkermansia muciniphila abundance was strongly and negatively affected by age and HFD feeding and to a lower extend Bilophila wadsworthia was the only taxa following an opposite trend. Different approaches, including multifactorial analysis, showed that these changes in Akkermansia muciniphila were robustly correlated with the expression of lipid metabolism and inflammation markers in adipose tissue, as well as several circulating parameters (i.e., glucose, insulin, triglycerides, leptin) from DIO mice. Thus, our data shows the existence of a link between gut Akkermansia muciniphila abundance and adipose tissue homeostasis on the onset of obesity, thus reinforcing the beneficial role of this bacterium on metabolism

Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

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

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Whey protein reduces early life weight gain in mice fed a high-fat diet.

An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P<0.001-0.05). Hereafter weight gain was similar resulting in a 15% lower final body weight in the whey group relative to casein (34.0±1.0 g vs. 40.2±1.3 g, P<0.001). Food intake was unaffected by protein source throughout the study period. Fasting insulin was lower in the whey group (P<0.01) and glucose clearance was improved after an oral glucose challenge (P<0.05). Plasma cholesterol was lowered by whey compared to casein (P<0.001). The composition of the fecal microbiota differed between high- and low-fat groups at 13 weeks (P<0.05) whereas no difference was seen between whey and casein. In conclusion, whey initially reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota composition. Further studies are needed to clarify the mechanisms behind the metabolic effects of whey

Increased Oral Detection, but Decreased Intestinal Signaling for Fats in Mice Lacking Gut Microbiota

Germ-free (GF) mice lacking intestinal microbiota are significantly leaner than normal (NORM) control mice despite consuming more calories. The contribution of microbiota on the recognition and intake of fats is not known. Thus, we investigated the preference for, and acceptance of, fat emulsions in GF and NORM mice, and associated changes in lingual and intestinal fatty acid receptors, intestinal peptide content, and plasma levels of gut peptides. GF and NORM C57Bl/6J mice were given 48-h two-bottle access to water and increasing concentrations of intralipid emulsions. Gene expression of the lingual fatty acid translocase CD36 and protein expression of intestinal satiety peptides and fatty-acid receptors from isolated intestinal epithelial cells were determined. Differences in intestinal enteroendocrine cells along the length of the GI tract were quantified. Circulating plasma satiety peptides reflecting adiposity and biochemical parameters of fat metabolism were also examined. GF mice had an increased preference and intake of intralipid relative to NORM mice. This was associated with increased lingual CD36 (P<0.05) and decreased intestinal expression of fatty acid receptors GPR40 (P<0.0001), GPR41 (P<0.0001), GPR43 (P<0.05), and GPR120 (P<0.0001) and satiety peptides CCK (P<0.0001), PYY (P<0.001), and GLP-1 (P<0.001). GF mice had fewer enteroendocrine cells in the ileum (P<0.05), and more in the colon (P<0.05), relative to NORM controls. Finally, GF mice had lower levels of circulating leptin and ghrelin (P<0.001), and altered plasma lipid metabolic markers indicative of energy deficits. Increased preference and caloric intake from fats in GF mice are associated with increased oral receptors for fats coupled with broad and marked decreases in expression of intestinal satiety peptides and fatty-acid receptors

Specific gut microbial, biological, and psychiatric profiling related to binge eating disorders: A cross-sectional study in obese patients

Background & aimsBinge eating disorder (BED) is a frequent eating disorder associated with obesity and co-morbidities including psychiatric pathologies, which represent a big health burden on the society.The biological processes related to BED remain unknown. Based on psychological testing, anthropometry, clinical biology, gut microbiota analysis and metabolomic assessment, we aimed to examine the complex biological and psychiatric profile of obese patients with and without BED.MethodsPsychological and biological characteristics (anthropometry, plasma biology, gut microbiota, blood pressure) of 101 obese subjects from the Food4Gut cohort were analysed to decipher the differences between BED and Non BED patients, classified based on the Questionnaire for Eating Disorder Diagnosis (Q-EDD). Microbial 16S rDNA sequencing and plasma non-targeted metabolomics (liquid chromatography-mass spectrometry) were performed in a subcohort of 91 and 39 patients respectively.ResultsBED subjects exhibited an impaired affect balance, deficits in inhibition and self-regulation together with marked alterations of eating behaviour (increased emotional and external eating). BED subjects displayed a lower blood pressure and hip circumference. A decrease in Akkermansia and Intestimonas as well as an increase in Bifidobacterium and Anaerostipes characterized BED subjects. Interestingly, metabolomics analysis revealed that BED subjects displayed a higher level of one food contaminants, Bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE.2H(2)O) and a food derived-metabolite the Isovalerylcarnitine.ConclusionsNon-targeted omics approaches allow to select specific microbial genera and two plasma metabolites that characterize BED obese patients. Further studies are needed to confirm their potential role as drivers or biomarkers of binge eating disorder

Restoring Specific Lactobacilli Levels Decreases Inflammation and Muscle Atrophy Markers in an Acute Leukemia Mouse Model

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

Resveratrol inhibits nonalcoholic fatty liver disease in rats

<p>Abstract</p> <p>Background</p> <p>The prevalence of nonalcoholic fatty liver disease (NAFLD) is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor α (TNF-α) production, lipid peroxidation and oxidative stress.</p> <p>Methods</p> <p>Male Wistar CRL: Wi (Han) (225 g) rats were randomized into three groups. A control group (n = 12) was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12) and resveratrol (n = 12) groups were given free access to feed (a high carbohydrate-fat free modified diet) and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-α in serum, hepatic malondialdehyde (MDA), oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase) and biochemical parameters were measured.</p> <p>Results</p> <p>Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P < 0.05). TNF-α and MDA levels were significantly increased in the steatosis group (TNF-α; 33.4 ± 5.2 vs 26.24 ± 3.47 pg/ml and MDA; 9.08 ± 0.8 vs 3.17 ± 1.45 μM respectively, <it>P </it>< 0.05). This was accompanied by increased superoxide dismutase, glutathione peroxidase and catalase and decreased nitric oxide synthase in the liver of resveratrol group significantly (<it>P </it>< 0.05 vs steatosis group). Bacterial translocation was not found in any of the groups. Glucose levels were decreased in the group of rats given resveratrol (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-α inhibition and antioxidant activities.</p

An Analysis of the Role of the Indigenous Microbiota in Cholesterol Gallstone Pathogenesis

Background and Aims: Cholesterol gallstone disease is a complex process involving both genetic and environmental variables. No information exists regarding what role if any the indigenous gastrointestinal microbiota may play in cholesterol gallstone pathogenesis and whether variations in the microbiota can alter cholesterol gallstone prevalence rates. Methods: Genetically related substrains (BALB/cJ and BALB/cJBomTac) and (BALB/AnNTac and BALB/cByJ) of mice obtained from different vendors were compared for cholesterol gallstone prevalence after being fed a lithogenic diet for 8 weeks. The indigenous microbiome was altered in these substrains by oral gavage of fecal slurries as adults, by cross-fostering to mice with divergent flora at <1day of age or by rederiving into a germ-free state. Results: Alterations in the indigenous microbiome altered significantly the accumulation of mucin gel and normalized gallbladder weight but did not alter cholesterol gallstone susceptibility in conventionally housed SPF mice. Germ-free rederivation rendered mice more susceptible to cholesterol gallstone formation. This susceptibility appeared to be largely due to alterations in gallbladder size and gallbladder wall inflammation. Colonization of germ-free mice with members of altered Schaedler flora normalized the gallstone phenotype to a level similar to conventionally housed mice. Conclusions: These data demonstrate that alterations in the gastrointestinal microbiome may alter aspects of cholesterol gallstone pathogenesis and that in the appropriate circumstances these changes may impact cholesterol cholelithogenesis.National Institutes of Health (U.S.) (Grant T32OD010978)National Institutes of Health (U.S.) (Grant P30ES002109)National Institutes of Health (U.S.) (Grant R01AT004326