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      Probiotics, Pre-biotics and Synbiotics in the Treatment of Pre-diabetes: A Systematic Review of Randomized Controlled Trials

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          Abstract

          Objectives: This study aimed to review the data from randomized controlled trials (RCTs) and identify evidence for microbiota's role and use of probiotics, pre-biotics, or synbiotics in pre-diabetes.

          Methods: RCTs of pro-, pre-, synbiotics for the treatment of pre-diabetes population will be summarized. We searched for EMBASE, MEDLINE, Web of Science, Cochrane Central, Clinical Trials (ClinicalTrials.gov) from inception to February 2021.

          Results: The gut microbiota influences host metabolic disorders via the modulation of metabolites, including short-chain fatty acids (SCFAs), the endotoxin lipopolysaccharides (LPS), bile acids (BA) and trimethylamine N-oxide (TMAO), as well as mediating the interaction between the gastrointestinal system and other organs. Due to the limited sources of studies, inconsistent outcomes between included studies. Probiotics can decrease glycated hemoglobin (HbA1c) and have the potential to improve post-load glucose levels. The supplementation of probiotics can suppress the rise of blood cholesterol, but the improvement cannot be verified. Pre-biotics are failed to show an evident improvement in glycemic control, but their use caused the changes in the composition of gut microbiota. A combination of probiotics and pre-biotics in the synbiotics supplementation is more effective than probiotics alone in glycemic control.

          Conclusion: In the current studies using probiotics, pre-biotics or synbiotics for the treatment of pre-diabetes, the benefits of modulating the abundance of gut microbiota were partially demonstrated. However, there is insufficient evidence to show significant benefits on glucose metabolism, lipid metabolism and body composition.

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          Most cited references86

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          Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation

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            A metagenome-wide association study of gut microbiota in type 2 diabetes.

            Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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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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                Author and article information

                Contributors
                Journal
                Front Public Health
                Front Public Health
                Front. Public Health
                Frontiers in Public Health
                Frontiers Media S.A.
                2296-2565
                26 March 2021
                2021
                : 9
                : 645035
                Affiliations
                [1] 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [2] 2Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, China
                Author notes

                Edited by: Vinod Tiwari, Indian Institute of Technology (BHU), India

                Reviewed by: Parameth Thiennimitr, Chiang Mai University, Thailand; Katia Sivieri, São Paulo State University, Brazil

                *Correspondence: Qiu Chen chenqiu1005@ 123456cdutcm.edu.cn

                This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Public Health

                Article
                10.3389/fpubh.2021.645035
                8032954
                33842424
                cbbcd9aa-8f64-4d3f-b0c2-b83819a6d71b
                Copyright © 2021 Wang, Yang, Qiu, Wen, Liu, Zhou and Chen.

                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
                : 22 December 2020
                : 03 March 2021
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 86, Pages: 10, Words: 7066
                Categories
                Public Health
                Systematic Review

                pre-diabetes,probiotics,pre-biotics,synbiotics,gut microbiota

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