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Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health

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  • Authors: Edward C. Deehan1, Rebbeca M. Duar2, Anissa M. Armet3, Maria Elisa Perez-Muñoz4, Mingliang Jin5, Jens Walter6,7
  • Editors: Robert Allen Britton8, Patrice D. Cani9
    Affiliations: 1: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E1; 2: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E1; 3: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E1; 4: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E1; 5: Department of Microbiology and Immunology, Northwestern Polytechnical University, Xi’an, Shaanxi, China 710065; 6: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E1; 7: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E1; 8: Baylor College of Medicine, Houston, TX 77030; 9: Université catholique de Louvain, Louvain Drug Research Institute, Brussels 1200, Belgium
  • Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0019-2017
  • Received 24 May 2017 Accepted 18 July 2017 Published 22 September 2017
  • Jens Walter, [email protected]
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  • Abstract:

    There is a clear association between the gastrointestinal (GI) microbiome and the development of chronic noncommunicable diseases, providing a rationale for the development of strategies that target the GI microbiota to improve human health. In this article, we discuss the potential of supplementing the human diet with nondigestible fermentable carbohydrates (NDFCs) to modulate the composition, structure, diversity, and metabolic potential of the GI microbiome in an attempt to prevent or treat human disease. The current concepts by which NDFCs can be administered to humans, including prebiotics, fermentable dietary fibers, and microbiota-accessible carbohydrates, as well as the mechanisms by which these carbohydrates exert their health benefits, are discussed. Epidemiological research presents compelling evidence for the health effects of NDFCs, with clinical studies providing further support for some of these benefits. However, rigorously designed human intervention studies with well-established clinical markers and microbial endpoints are still essential to establish (i) the clinical efficiency of specific NDFCs, (ii) the causal role of the GI microbiota in these effects, (iii) the underlying mechanisms involved, and (iv) the degree by which inter-individual differences between GI microbiomes influence these effects. Such studies would provide the mechanistic understanding needed for a systematic application of NDFCs to improve human health via GI microbiota modulation while also allowing the personalization of these dietary strategies.

  • Citation: Deehan E, Duar R, Armet A, Perez-Muñoz M, Jin M, Walter J. 2017. Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health. Microbiol Spectrum 5(5):BAD-0019-2017. doi:10.1128/microbiolspec.BAD-0019-2017.


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There is a clear association between the gastrointestinal (GI) microbiome and the development of chronic noncommunicable diseases, providing a rationale for the development of strategies that target the GI microbiota to improve human health. In this article, we discuss the potential of supplementing the human diet with nondigestible fermentable carbohydrates (NDFCs) to modulate the composition, structure, diversity, and metabolic potential of the GI microbiome in an attempt to prevent or treat human disease. The current concepts by which NDFCs can be administered to humans, including prebiotics, fermentable dietary fibers, and microbiota-accessible carbohydrates, as well as the mechanisms by which these carbohydrates exert their health benefits, are discussed. Epidemiological research presents compelling evidence for the health effects of NDFCs, with clinical studies providing further support for some of these benefits. However, rigorously designed human intervention studies with well-established clinical markers and microbial endpoints are still essential to establish (i) the clinical efficiency of specific NDFCs, (ii) the causal role of the GI microbiota in these effects, (iii) the underlying mechanisms involved, and (iv) the degree by which inter-individual differences between GI microbiomes influence these effects. Such studies would provide the mechanistic understanding needed for a systematic application of NDFCs to improve human health via GI microbiota modulation while also allowing the personalization of these dietary strategies.

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CNCDs that are associated with the GI microbiome and diets low in NDC. An industrialized lifestyle is associated with an increased prevalence of multiple CNCDs ( 15 ). Most of these diseases have now clearly been associated with the GI microbiome (pathology in animal models is dramatically different under germfree conditions, and the GI microbiome displays a dysbiosis in humans suffering from the disease). The Venn diagram designates CNCDs that are associated with the GI microbiome ( 2 , 221 , 247 , 248 ) and a diet low in NDCs ( 13 , 107 , 244 ). NAFLD, nonalcoholic fatty liver disease.

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0019-2017
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Categories of NDCs. NDCs are a heterogeneous group of compounds that display diverse chemical structures, which is the basis for their categorization alongside their origin ( 24 , 70 , 71 ). Nondigestible oligosaccharides are NDCs composed of three to nine monosaccharides and are from either plant or animal origin, as well as chemically synthesized.

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0019-2017
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Mechanisms by which the metabolism of NDFCs by the GI microbiota modulates host health. NDFCs are fermented by the GI microbiota to SCFAs, which upon absorption into enterocytes can activate intestinal GNG, leading to improved satiety and glucose homeostasis. SCFAs can further stimulate enteroendocrine L-cells to secrete PYY, GLP-1, and GLP-2. Both PYY and GLP-1 act as satiety hormones, while GLP-1 also promotes glucose tolerance. Meanwhile, the secretion of GLP-2 enhances intestinal barrier function by upregulating the expression of tight junction proteins. SCFAs further enhance the intestinal barrier by stimulating mucin secretion from goblet cells, which aids in reducing the translocation of LPS through the intestinal epithelium, consequently reducing inflammation. Additionally, SCFAs exert immunomodulatory effects by regulating the production of antimicrobial peptides, the expansion of regulatory T-cells, and myeloid cell function to inhibit inflammation. Moreover, SCFAs signal to organs distant from the GI tract, such as white adipose tissue, where they may act on adipocytes promoting the secretion of leptin, another anorectic hormone. Furthermore, the presence of NDFCs inhibits the production of potentially detrimental metabolites from the fermentation of dietary proteins through lowering intestinal pH. AMP, antimicrobial peptides, BCFAs, branched-chain fatty acids; CVD, cardiovascular disease; GLP, glucagon-like peptide; GNG, gluconeogenesis; LPS, lipopolysaccharides; PYY, peptide tyrosine tyrosine; SCFAs, short-chain fatty acids; T2D, type 2 diabetes; Tregs, regulatory T-cells.

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0019-2017
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