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      Talking microbes: When gut bacteria interact with diet and host organs

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          Abstract

          Obesity and diabetes have reached epidemic proportions. Evidence suggests that besides dietary habits and physical activity, other environmental factors, such as gut microbes, are recognized as additional partners implicated in the control of energy homeostasis. Studies on the human gut microbiota have shown that the general population can be stratified on the sole basis of three dominant bacteria (i.e., the concept of enterotypes), while some others have suggested categorizing the population according to their microbiome gene richness. Both aspects have been strengthened by recent studies investigating the impact of nutrients (e.g., dietary fibers, fat feeding) and dietary habits (i.e., vegans versus omnivores) of different populations. Using preclinical models, quite a few novel mechanisms have been proposed in these gut microbiota–host interactions, including the role of novel bacteria, the regulation of antimicrobial peptide production, the maintenance of the gut barrier function and intestinal innate immunity. In this review, we discuss several of the aforementioned aspects. Nonetheless, determining the overall mechanisms by which microbes dialogue with host cells will require further investigations before anticipating the development of next‐generation nutritional interventions using prebiotics, probiotics, synbiotics, or even specific nutrients for promoting health benefits.

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          Most cited references40

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          High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway

          Background & Aims While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet. Methods C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high–fat (60 kcal % fat) diet (HFD) for 8 weeks. Results HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice. Conclusions HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.
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            Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice

            OBJECTIVE To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice. RESEARCH DESIGN AND METHODS Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models. RESULTS In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat–fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters. CONCLUSIONS We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.
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              Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity

              The gut microbiota is involved in metabolic and immune disorders associated with obesity and type 2 diabetes. We previously demonstrated that prebiotic treatment may significantly improve host health by modulating bacterial species related to the improvement of gut endocrine, barrier and immune functions. An analysis of the gut metagenome is needed to determine which bacterial functions and taxa are responsible for beneficial microbiota–host interactions upon nutritional intervention. We subjected mice to prebiotic (Pre) treatment under physiological (control diet: CT) and pathological conditions (high-fat diet: HFD) for 8 weeks and investigated the production of intestinal antimicrobial peptides and the gut microbiome. HFD feeding significantly decreased the expression of regenerating islet-derived 3-gamma (Reg3g) and phospholipase A2 group-II (PLA2g2) in the jejunum. Prebiotic treatment increased Reg3g expression (by ∼50-fold) and improved intestinal homeostasis as suggested by the increase in the expression of intectin, a key protein involved in intestinal epithelial cell turnover. Deep metagenomic sequencing analysis revealed that HFD and prebiotic treatment significantly affected the gut microbiome at different taxonomic levels. Functional analyses based on the occurrence of clusters of orthologous groups (COGs) of proteins also revealed distinct profiles for the HFD, Pre, HFD-Pre and CT groups. Finally, the gut microbiota modulations induced by prebiotics counteracted HFD-induced inflammation and related metabolic disorders. Thus, we identified novel putative taxa and metabolic functions that may contribute to the development of or protection against the metabolic alterations observed during HFD feeding and HFD-Pre feeding.
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                Author and article information

                Journal
                Mol Nutr Food Res
                Mol Nutr Food Res
                10.1002/(ISSN)1613-4133
                MNFR
                Molecular Nutrition & Food Research
                John Wiley and Sons Inc. (Hoboken )
                1613-4125
                1613-4133
                January 2016
                26 August 2015
                : 60
                : 1 , Obesity: Dysfunction, regulation and control ( doiID: 10.1002/mnfr.60.1 )
                : 58-66
                Affiliations
                [ 1 ] Metabolism and Nutrition Research Group WELBIO‐ Walloon Excellence in Life Sciences and BIOtechnology Louvain Drug Research InstituteUniversité catholique de Louvain BrusselsBelgium
                Author notes
                [*] [* ] Correspondence: Patrice D. Cani

                E‐mail: patrice.cani@ 123456uclouvain.be

                Article
                MNFR2446
                10.1002/mnfr.201500406
                5014210
                26178924
                5020498a-13ad-4e0d-890c-1536000c72db
                © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.

                This is an open access article under the terms of the Creative Commons Attribution‐Non‐Commercial‐NoDerivs Licence, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 26 May 2015
                : 03 July 2015
                : 07 July 2015
                Page count
                Pages: 9
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                mnfr2446
                January 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:09.09.2016

                Nutrition & Dietetics
                diabetes,energy metabolism,gut microbiota,innate immunity,obesity
                Nutrition & Dietetics
                diabetes, energy metabolism, gut microbiota, innate immunity, obesity

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