Chapter 20 : Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health

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Vertebrates have evolved with dense microbial populations in their gastrointestinal (GI) tract (referred to as the GI microbiome) that contribute to performance and health of the host ( ). Although symbiotic in nature, animal experiments have established that the GI microbiota plays a causative role in the development of chronic noncommunicable diseases (CNCDs) such as obesity, diabetes, cardiovascular disease, colon cancer, autism, autoimmune diseases, allergies, and other atopic diseases including asthma ( Fig. 1 ) ( ). CNCDs are often associated with microbial dysbiosis, which is typically characterized by a reduced diversity, a bloom of facultative taxa (such as enterobacteria), and a lower output of beneficial metabolites ( ). These associations provide a clear rationale for the development of strategies that modulate GI microbiome structure and function for the prevention of CNCDs ( ).

Citation: Deehan E, Duar R, Armet A, Perez-Muñoz M, Jin M, Walter J. 2018. Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health, p 453-483. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0019-2017
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Figure 1

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 ( ). 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 ( ) and a diet low in NDCs ( ). NAFLD, nonalcoholic fatty liver disease.

Citation: Deehan E, Duar R, Armet A, Perez-Muñoz M, Jin M, Walter J. 2018. Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health, p 453-483. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0019-2017
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Figure 2

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 ( ). Nondigestible oligosaccharides are NDCs composed of three to nine monosaccharides and are from either plant or animal origin, as well as chemically synthesized.

Citation: Deehan E, Duar R, Armet A, Perez-Muñoz M, Jin M, Walter J. 2018. Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health, p 453-483. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0019-2017
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Figure 3

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.

Citation: Deehan E, Duar R, Armet A, Perez-Muñoz M, Jin M, Walter J. 2018. Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health, p 453-483. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0019-2017
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