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      Targeting Gut Microbiota for the Prevention and Management of Diabetes Mellitus by Dietary Natural Products

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          Abstract

          Diabetes mellitus is one of the biggest public health concerns worldwide, which includes type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and other rare forms of diabetes mellitus. Accumulating evidence has revealed that intestinal microbiota is closely associated with the initiation and progression of diabetes mellitus. In addition, various dietary natural products and their bioactive components have exhibited anti-diabetic activity by modulating intestinal microbiota. This review addresses the relationship between gut microbiota and diabetes mellitus, and discusses the effects of natural products on diabetes mellitus and its complications by modulating gut microbiota, with special attention paid to the mechanisms of action. It is hoped that this review paper can be helpful for better understanding of the relationships among natural products, gut microbiota, and diabetes mellitus.

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          Gut microbial metabolites in obesity, NAFLD and T2DM

          Emanuel E Canfora, Ruth Meex, Koen Venema … (2019)
          Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.
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            Type 1 diabetes

            Carmella Evans-Molina, Richard Oram, Linda A DiMeglio (2018)
            Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.
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              PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD

              Barbara Gross, Michal Pawlak, Philippe Lefebvre … (2017)
              Obesity is a worldwide epidemic that predisposes individuals to cardiometabolic complications, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), which are all related to inappropriate ectopic lipid deposition. Identification of the pathogenic molecular mechanisms and effective therapeutic approaches are highly needed. The peroxisome proliferator-activated receptors (PPARs) modulate several biological processes that are perturbed in obesity, including inflammation, lipid and glucose metabolism and overall energy homeostasis. Here, we review how PPARs regulate the functions of adipose tissues, such as adipogenesis, lipid storage and adaptive thermogenesis, under healthy and pathological conditions. We also discuss the clinical use and mechanism of PPAR agonists in the treatment of obesity comorbidities such as dyslipidaemia, T2DM and NAFLD. First generation PPAR agonists, primarily those acting on PPARγ, are associated with adverse effects that outweigh their clinical benefits, which led to the discontinuation of their development. An improved understanding of the physiological roles of PPARs might, therefore, enable the development of safe, new PPAR agonists with improved therapeutic potential.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Foods
                Journal ID (iso-abbrev): Foods
                Journal ID (publisher-id): foods
                Title: Foods
                Publisher: MDPI
                ISSN (Electronic): 2304-8158
                Publication date (Electronic): 25 September 2019
                Publication date Collection: October 2019
                Volume: 8
                Issue: 10
                Electronic Location Identifier: 440
                Affiliations
                [1 ]Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; liby35@ 123456mail2.sysu.edu.cn (B.-Y.L.); xuxy53@ 123456mail2.sysu.edu.cn (X.-Y.X.); mengjm@ 123456mail2.sysu.edu.cn (J.-M.M.); shangao@ 123456mail2.sysu.edu.cn (A.S.); maoqq@ 123456mail2.sysu.edu.cn (Q.-Q.M.)
                [2 ]Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China
                [3 ]Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
                [4 ]School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; sqctp8@ 123456ujs.edu.cn
                Author notes
                [* ]Correspondence: ganrenyou@ 123456caas.cn (R.-Y.G.); lihuabin@ 123456mail.sysu.edu.cn (H.-B.L.); Tel.: +86-28-8020-3191 (R.-Y.G.); +86-20-873-323-91 (H.-B.L.)
                Author information
                https://orcid.org/0000-0003-2332-8554
                Article
                Publisher ID: foods-08-00440
                DOI: 10.3390/foods8100440
                PMC ID: 6835620
                PubMed ID: 31557941
                SO-VID: 702325f6-dfd1-44c9-8dae-c1c9cf40557c
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 17 August 2019
                Date accepted : 23 September 2019
                Categories
                Subject: Review

                Keywords: gut microbiota,natural products,diabetes mellitus,complications,mechanisms
                Data availability:
                Keywords: gut microbiota, natural products, diabetes mellitus, complications, mechanisms

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