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      The Metabolic Role and Therapeutic Potential of the Microbiome

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          Abstract

          We are host to an assembly of microorganisms that vary in structure and function along the length of the gut and from the lumen to the mucosa. This ecosystem is collectively known as the gut microbiota and significant efforts have been spent during the past 2 decades to catalog and functionally describe the normal gut microbiota and how it varies during a wide spectrum of disease states. The gut microbiota is altered in several cardiometabolic diseases and recent work has established microbial signatures that may advance disease. However, most research has focused on identifying associations between the gut microbiota and human diseases states and to investigate causality and potential mechanisms using cells and animals. Since the gut microbiota functions on the intersection between diet and host metabolism, and can contribute to inflammation, several microbially produced metabolites and molecules may modulate cardiometabolic diseases. Here we discuss how the gut bacterial composition is altered in, and can contribute to, cardiometabolic disease, as well as how the gut bacteria can be targeted to treat and prevent metabolic diseases.

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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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            Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

            An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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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
                Endocr Rev
                Endocr Rev
                edrv
                Endocrine Reviews
                Oxford University Press (US )
                0163-769X
                1945-7189
                October 2022
                30 January 2022
                30 January 2022
                : 43
                : 5
                : 907-926
                Affiliations
                Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg , Sweden
                Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg , Sweden
                Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen , Denmark
                Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology , Gothenburg, Sweden
                Author notes
                Correspondence: Louise E. Olofsson, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Bruna Stråket 16, 413 45 Gothenburg, Sweden. Email: Louise.Olofsson@ 123456wlab.gu.se
                Fredrik Bäckhed, Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Bruna Stråket 16, 413 45 Gothenburg, Sweden. Email: Fredrik@ 123456wlab.gu.se .
                Author information
                https://orcid.org/0000-0002-2302-2005
                https://orcid.org/0000-0002-4871-8818
                Article
                bnac004
                10.1210/endrev/bnac004
                9512151
                35094076
                02eed3d7-3553-4168-aa0f-33fe57e3cfe1
                © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 15 September 2021
                : 22 December 2021
                : 09 February 2022
                Page count
                Pages: 21
                Funding
                Funded by: Swedish Research Council, DOI 10.13039/501100004359;
                Award ID: 2019-01599
                Funded by: AFA insurances;
                Award ID: 160337
                Funded by: Leducq Foundation, DOI 10.13039/501100001674;
                Award ID: 17CVD01
                Funded by: NovoNordisk Foundation;
                Award ID: NNF15OC0016798
                Funded by: Swedish Heart Lung Foundation;
                Award ID: 20180600
                Funded by: Knut and Alice Wallenberg Foundation, DOI 10.13039/501100004063;
                Award ID: 2017.0026
                Funded by: Swedish government and the county councils;
                Funded by: ALF-agreement;
                Award ID: ALFGBG- 718101
                Categories
                Review
                AcademicSubjects/MED00250

                gut microbiome,obesity,type 2 diabetes,cardiovascular disease,metabolites,therapeutics,scfa,intestine,liver,brain,adipose tissue

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