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      The Influence of the Gut Microbiome on Host Metabolism Through the Regulation of Gut Hormone Release

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          Abstract

          The microbial community of the gut conveys significant benefits to host physiology. A clear relationship has now been established between gut bacteria and host metabolism in which microbial-mediated gut hormone release plays an important role. Within the gut lumen, bacteria produce a number of metabolites and contain structural components that act as signaling molecules to a number of cell types within the mucosa. Enteroendocrine cells within the mucosal lining of the gut synthesize and secrete a number of hormones including CCK, PYY, GLP-1, GIP, and 5-HT, which have regulatory roles in key metabolic processes such as insulin sensitivity, glucose tolerance, fat storage, and appetite. Release of these hormones can be influenced by the presence of bacteria and their metabolites within the gut and as such, microbial-mediated gut hormone release is an important component of microbial regulation of host metabolism. Dietary or pharmacological interventions which alter the gut microbiome therefore pose as potential therapeutics for the treatment of human metabolic disorders. This review aims to describe the complex interaction between intestinal microbiota and their metabolites and gut enteroendocrine cells, and highlight how the gut microbiome can influence host metabolism through the regulation of gut hormone release.

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          Diet rapidly and reproducibly alters the human gut microbiome

          Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut 1–5 , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals 2 , reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease 6 . In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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            An obesity-associated gut microbiome with increased capacity for energy harvest.

            The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
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              From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

              A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                16 April 2019
                2019
                : 10
                : 428
                Affiliations
                [1] 1Molecular and Cellular Physiology Laboratory, College of Medicine and Public Health, Flinders University , Adelaide, SA, Australia
                [2] 2Microbiome Research Laboratory, Flinders University , Adelaide, SA, Australia
                [3] 3Infection and Immunity, South Australian Health and Medical Research Institute , Adelaide, SA, Australia
                [4] 4Nutrition and Metabolism, South Australian Health and Medical Research Institute , Adelaide, SA, Australia
                Author notes

                Edited by: Tongzhi Wu, The University of Adelaide, Australia

                Reviewed by: Enzo Spisni, University of Bologna, Italy; P. Trayhurn, University of Liverpool, United Kingdom

                *Correspondence: Damien J. Keating, damien.keating@ 123456flinders.edu.au

                This article was submitted to Clinical and Translational Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2019.00428
                6477058
                31057420
                b5984f03-2a48-44e7-a3c9-b18554ad63cf
                Copyright © 2019 Martin, Sun, Rogers and Keating.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 January 2019
                : 27 March 2019
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 142, Pages: 11, Words: 0
                Categories
                Physiology
                Mini Review

                Anatomy & Physiology
                enteroendocrine cells,microbiome,metabolism,glp-1,pyy,gip,serotonin,cck
                Anatomy & Physiology
                enteroendocrine cells, microbiome, metabolism, glp-1, pyy, gip, serotonin, cck

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