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      Potential mediators linking gut bacteria to metabolic health: a critical view

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          Abstract

          Growing evidence suggests that the bacteria present in our gut may play a role in mediating the effect of genetics and lifestyle on obesity and metabolic diseases. Most of the current literature on gut bacteria consists of cross‐sectional and correlative studies, rendering it difficult to make any causal inferences as to the influence of gut bacteria on obesity and related metabolic disorders. Interventions with germ‐free animals, treatment with antibiotic agents, and microbial transfer experiments have provided some evidence that disturbances in gut bacteria may causally contribute to obesity‐related insulin resistance and adipose tissue inflammation. Several potential mediators have been hypothesized to link the activity and composition of gut bacteria to insulin resistance and adipose tissue function, including lipopolysaccharide, angiopoietin‐like protein 4, bile acids and short‐chain fatty acids. In this review we critically evaluate the current evidence related to the direct role of gut bacteria in obesity‐related metabolic perturbations, with a focus on insulin resistance and adipose tissue inflammation. It is concluded that the knowledge base in support of a role for the gut microbiota in metabolic regulation and in particular insulin resistance and adipose tissue inflammation needs to be strengthened.

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          Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors.

          In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases.
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            Pleiotropic roles of bile acids in metabolism.

            Enzymatic oxidation of cholesterol generates numerous distinct bile acids that function both as detergents that facilitate digestion and absorption of dietary lipids, and as hormones that activate four distinct receptors. Activation of these receptors alters gene expression in multiple tissues, leading to changes not only in bile acid metabolism but also in glucose homeostasis, lipid and lipoprotein metabolism, energy expenditure, intestinal motility and bacterial growth, inflammation, liver regeneration, and hepatocarcinogenesis. This review covers the roles of specific bile acids, synthetic agonists, and their cognate receptors in controlling these diverse functions, as well as their current use in treating human diseases. Copyright © 2013 Elsevier Inc. All rights reserved.
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              The importance of the viable but non-culturable state in human bacterial pathogens

              Many bacterial species have been found to exist in a viable but non-culturable (VBNC) state since its discovery in 1982. VBNC cells are characterized by a loss of culturability on routine agar, which impairs their detection by conventional plate count techniques. This leads to an underestimation of total viable cells in environmental or clinical samples, and thus poses a risk to public health. In this review, we present recent findings on the VBNC state of human bacterial pathogens. The characteristics of VBNC cells, including the similarities and differences to viable, culturable cells and dead cells, and different detection methods are discussed. Exposure to various stresses can induce the VBNC state, and VBNC cells may be resuscitated back to culturable cells under suitable stimuli. The conditions that trigger the induction of the VBNC state and resuscitation from it are summarized and the mechanisms underlying these two processes are discussed. Last but not least, the significance of VBNC cells and their potential influence on human health are also reviewed.
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                Author and article information

                Contributors
                sander.kersten@wur.nl
                Journal
                J Physiol
                J. Physiol. (Lond.)
                10.1111/(ISSN)1469-7793
                TJP
                jphysiol
                The Journal of Physiology
                John Wiley and Sons Inc. (Hoboken )
                0022-3751
                1469-7793
                03 August 2016
                15 January 2017
                03 August 2016
                : 595
                : 2 ( doiID: 10.1113/tjp.2017.595.issue-2 )
                : 477-487
                Affiliations
                [ 1 ] Nutrition, Metabolism and Genomics Group, Division of Human NutritionWageningen University WageningenThe Netherlands
                Author notes
                [*] [* ] Corresponding author S. Kersten: Nutrition, Metabolism and Genomics group, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands. Email: sander.kersten@ 123456wur.nl
                Article
                TJP7423
                10.1113/JP272476
                5233664
                27418465
                b8bffcbb-c228-411a-a447-2bec9eb23a3c
                © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, 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
                : 21 March 2016
                : 01 July 2016
                Page count
                Figures: 0, Tables: 0, Pages: 11, Words: 8312
                Funding
                Funded by: Netherlands Heart Foundation IN‐CONTROL
                Award ID: CVON2012‐03
                Categories
                Cellular and Molecular Physiology
                Adipose Tissue and Obesity
                Endocrine and Metabolic Conditons, Disorders and Treatments
                Topical Review
                Special section reviews: Influence of the microbiota on host physiology ‐ moving beyond the gut
                Editor's Choice
                Custom metadata
                2.0
                tjp7423
                15 January 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.1 mode:remove_FC converted:12.01.2017

                Human biology
                adipose tissue inflammation,angiopoietin‐like protein 4,bile acids,gut bacteria,insulin resistance,lipopolysaccharide,short‐chain fatty acids

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