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      Gut microbiota functions: metabolism of nutrients and other food components

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          Abstract

          The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays.

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          A core gut microbiome in obese and lean twins

          The human distal gut harbors a vast ensemble of microbes (the microbiota) that provide us with important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides1–6. Studies of a small number of unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes6–8, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is utilized and stored3–5. To address the question of how host genotype, environmental exposures, and host adiposity influence the gut microbiome, we have characterized the fecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person’s gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable ‘core microbiome’ at the gene, rather than at the organismal lineage level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity, and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiologic states (obese versus lean).
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            Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

            Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
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              Formation of propionate and butyrate by the human colonic microbiota

              The human gut microbiota ferments dietary non-digestible carbohydrates into short-chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health-promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross-feeding of intermediary metabolites (in particular lactate, succinate and 1,2-propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.
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                Author and article information

                Contributors
                +32 (0)2 775 91 44 , publications@ilsieurope.be , i.rowland@reading.ac.uk
                g.r.gibson@reading.ac.uk
                Almut.heinken@uni.lu
                K.Scott@abdn.ac.uk
                j.swann@imperial.ac.uk
                ines.thiele@uni.lu
                kieran.tuohy@fmach.it
                Journal
                Eur J Nutr
                Eur J Nutr
                European Journal of Nutrition
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1436-6207
                1436-6215
                9 April 2017
                9 April 2017
                2018
                : 57
                : 1
                : 1-24
                Affiliations
                [1 ]ISNI 0000 0004 0457 9566, GRID grid.9435.b, Department of Food and Nutritional Sciences, , University of Reading, ; Whiteknights, Reading, RG6 6AP UK
                [2 ]ISNI 0000 0001 2295 9843, GRID grid.16008.3f, Luxembourg Centre for Systems Biomedicine, , University of Luxembourg, ; Campus Belval, Avenue des Hauts Fourneaux 7, 4362 Esch-sur-Alzette, Luxembourg
                [3 ]ISNI 0000 0004 1936 7291, GRID grid.7107.1, The Rowett Institute, , University of Aberdeen, ; Foresterhill, Aberdeen, AB25 2ZD UK
                [4 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Division of Computational and Systems Medicine, Department of Surgery and Cancer, , Imperial College London, ; London, SW7 2AZ UK
                [5 ]ISNI 0000 0004 1755 6224, GRID grid.424414.3, Nutrition and Nutrigenomics Unit, Department of Food Quality and Nutrition, Research and Innovation Centre, , Fondazione Edmund Mach, ; Via E. Mach, 1, Trento, 38010 Italy
                Article
                1445
                10.1007/s00394-017-1445-8
                5847071
                28393285
                9c8cd8e8-4471-43d4-af1e-63358d6c113e
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 31 December 2016
                : 23 March 2017
                Funding
                Funded by: International Life Sciences Institute Europe
                Categories
                Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Nutrition & Dietetics
                gut microbiota,microbiome,microbial metabolism,food components,methodology
                Nutrition & Dietetics
                gut microbiota, microbiome, microbial metabolism, food components, methodology

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