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      Using probiotics for type 2 diabetes mellitus intervention: Advances, questions, and potential

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          Abstract

          <p class="first" id="d5522011e152">Type 2 diabetes mellitus (T2DM) has become one of the most prevalent diseases on earth and several treatments have been developed. However, the current intervention approaches have not been as effective as expected. One promising supplementary strategy is the use of probiotics through direct or indirect approaches. Probiotics are microbial food cultures conferring health-promoting properties. In this review, we summarized the current theories and mechanisms of T2DM intervention using probiotics and hypothesize that probiotics intervene T2DM during its onsetting, developing, and complicating. For the first time, we comprehensively analyzed T2DM intervention in animal models using both wide-type probiotics in different forms and using recombinant probiotics. Then, probiotic intervention in T2DM patients was reviewed and the main results were compared with that obtained from animal studies. Finally yet importantly, remaining questions that are important such as in which form and in which state, as well as the future potential of probiotic intervention in T2DM were discussed from a perspective of food microbiologists. In conclusion, probiotic intervention in T2DM is promising but there are still many important issues unsolved yet. Critical review of the advances, questions, and potential of probiotic intervention in T2DM promotes the development of this approach for further application in humans. </p>

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          Most cited references132

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          Metabolic endotoxemia initiates obesity and insulin resistance.

          Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.
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            Human gut microbes impact host serum metabolome and insulin sensitivity.

            Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
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              Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.

              Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of β-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Critical Reviews in Food Science and Nutrition
                Critical Reviews in Food Science and Nutrition
                Informa UK Limited
                1040-8398
                1549-7852
                February 21 2020
                January 11 2019
                February 21 2020
                : 60
                : 4
                : 670-683
                Affiliations
                [1 ] College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou, China;
                [2 ] College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, China;
                [3 ] College of Life Sciences, Huazhong University of Science and Technology, Wuhan, China;
                [4 ] Zhoukou Maternal and Child Health Care Hospital, Zhoukou, China;
                [5 ] College of Life Sciences, Henan Institute of Science and Technology, Xinxiang, China
                Article
                10.1080/10408398.2018.1547268
                30632770
                ac8aa158-92a8-4515-ad9e-789d69460003
                © 2020
                History

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