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Journal ArticleDOI: 10.1007/S00394-021-02520-4

Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes.

02 Mar 2021-European Journal of Nutrition (Springer Berlin Heidelberg)-Vol. 60, Iss: 5, pp 2361-2379
Abstract: Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions. This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D. There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.

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Topics: Glucose homeostasis (55%), Synbiotics (53%), Insulin resistance (53%)
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5 results found


Journal ArticleDOI: 10.1016/J.FCT.2021.112235
Xiao-Xiao Li1, Xiu-Xiu Zhang1, Rui Zhang1, Zhi-Jing Ni2  +8 moreInstitutions (3)
Abstract: We explored the effect of carboxymethylated wheat bran dietary fibers (DFs) on mice with type 2 diabetes (T2D) (induced by HFD combined with STZ) and their possible hypoglycemic mechanism. After feeding the diabetic mice with modified DFs for four weeks, the DFs had lipid lowering and anti-hyperglycemic effect, via increasing the levels of insulin, GLP-1, PYY, and SCFAs in diabetic mice, and improving the histopathology of liver and pancreas. qRT-PCR results showed that the intake of DFs up-regulated the expression levels of G6Pase and Prkce, and down regulated the expression levels of Glut2 and InsR in the liver of diabetic mice. It is suggested that DFs may play a role by inhibiting 1,2-DAG-PKCe pathway, improving insulin receptor activity and insulin signal transduction. 16 S rDNA high-throughput sequencing results showed that the DFs significantly improved the relative abundance of Akkermansia muciniphila, increased the diversity of gut microbiota and reduced the ratio of Firmicutes to Bacteroidetes, thus promoting the hypoglycemic and hypolipidemic effect on diabetic mice. Our study can foster the further understanding of the gut modulatory biomarkers and related metabolites, and may extend the basis for DFs as a potential dietary intervention to prevent or treat the T2D.

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Topics: Insulin (55%), Akkermansia muciniphila (53%), Diabetes mellitus (51%)

6 Citations


Open accessJournal ArticleDOI: 10.3389/FENDO.2021.669448
Abstract: Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology's multifactorial nature makes patient management, including lifelong drug therapy and lifestyle modification, extremely challenging. Currently, there is growing evidence about the effectiveness of using herbal supplements in preventing and controlling DM. Curcumin is a bioactive component found Curcuma longa, which exhibits several physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and anti-diabetic activities. For these reasons, our objective is to systematically review the effects of Curcuma longa or curcumin on DM. Databases such as PUBMED and EMBASE were searched, and the final selection included sixteen studies that fulfilled the inclusion criteria. The results showed that curcumin's anti-diabetic activity might be due to its capacity to suppress oxidative stress and inflammatory process. Also, it significantly reduces fasting blood glucose, glycated hemoglobin, and body mass index. Nanocurcumin is also associated with a significant reduction in triglycerides, VLDL-c, total cholesterol, LDL-c, HDL-c, serum C reactive protein, and plasma malonaldehyde. Therefore, it can be considered in the therapeutic approach of patients with DM.

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2 Citations


Journal ArticleDOI: 10.1097/MCO.0000000000000782
Abstract: Purpose of review To highlight emerging evidence challenging traditional recommendations to increase carbohydrate intake to optimize performance at high altitude. Recent findings Several studies have now clearly demonstrated that, compared with sea level, exogenous carbohydrate oxidation during aerobic exercise is blunted in lowlanders during initial exposure to high altitude. There is also no apparent ergogenic effect of ingesting carbohydrate during aerobic exercise on subsequent performance at high altitude, either initially after arriving or even after up to 22 days of acclimatization. The inability to oxidize and functionally benefit from exogenous carbohydrate intake during exercise after arriving at high altitude coincides with hyperinsulinemia, accelerated glycogenolysis, and reduced peripheral glucose uptake. Collectively, these responses are consistent with a hypoxia-mediated metabolic dysregulation reflective of insulin resistance. Parallel lines of evidence have also recently demonstrated roles for the gut microbiome in host metabolism, bioenergetics, and physiologic responses to high altitude, implicating the gut microbiome as one potential mediator of hypoxia-mediated metabolic dysregulation. Summary Identification of novel and well tolerated nutrition and/or pharmacological approaches for alleviating hypoxia-mediated metabolic dysregulation and enhancing exogenous carbohydrate oxidation may be more effective for optimizing performance of lowlanders newly arrived at high altitude than traditional carbohydrate recommendations.

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Open accessJournal ArticleDOI: 10.2147/DMSO.S284401
Abstract: The ongoing obesity epidemic in children and adolescents has greatly increased the prevalence of related comorbidities. Prediabetes is defined based on levels of fasting glucose, oral glucose tolerance tests or hemoglobin A1c, that are intermediate between normal levels and thresholds that define type 2 diabetes mellitus (T2DM). As such, prediabetes represents a sign of early pathophysiology preceding T2DM development. Recent analyses of data from US adolescents estimate prediabetes to be present in 4-23% of adolescents, depending on criteria used, with other studies finding an 8% risk of progression from prediabetes to T2DM over a 3-year period. These data support the importance of intervention to avoid long-term sequelae, focusing on reducing degree of obesity and insulin resistance. Lifestyle modification, with increases in physical activity and dietary improvements, remains the first-line approach. Other interventions are based on additional long-term risks and range from metformin treatment for more moderate cases of prediabetes to bariatric surgery for adolescents with severe obesity and comorbidities. As data accumulate regarding sequelae of T2DM in adolescents, there remains a critical need for prevention of obesity and T2DM throughout childhood, and prediabetes should be a trigger for improving this risk profile.

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Topics: Prediabetes (63%), Diabetes mellitus (52%), Type 2 Diabetes Mellitus (52%) ... show more

Open accessJournal ArticleDOI: 10.3390/NU13092983
27 Aug 2021-Nutrients
Abstract: Insulin resistance leads to the onset of medical conditions such as type 2 diabetes, and its development is associated with the alteration in the gut microbiota. Although it has been demonstrated that supplementation with prebiotics modulates the gut microbiota, limited evidence is available for effects of prebiotics on insulin resistance, especially for humans. We investigated the prebiotic effect of 1-kestose supplementation on fasting insulin concentration in obesity-prone humans and rats. In the preliminary study using rats, the hyperinsulinemia induced by high-fat diet was suppressed by intake of water with 2% (w/v) 1-kestose. In the clinical study using obese-prone volunteers, the fasting serum insulin level was significantly reduced from 6.5 µU/mL (95% CI, 5.5-7.6) to 5.3 (4.6-6.0) by the 12-week intervention with supplementation of 10 g 1-kestose/day, whereas it was not changed by the intervention with placebo (6.2 µU/mL (5.4-7.1) and 6.5 (5.5-7.6) before and after intervention, respectively). The relative abundance of fecal Bifidobacterium was significantly increased to 0.3244 (SD, 0.1526) in 1-kestose-supplemented participants compared to that in control participants (0.1971 (0.1158)). These results suggest that prebiotic intervention using 1-kestose may potentially ameliorate insulin resistance in overweight humans via the modulation of the gut microbiota. UMIN 000028824.

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Topics: Insulin resistance (59%), Prebiotic (55%), Hyperinsulinemia (54%) ... show more
References
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206 results found


Open accessJournal ArticleDOI: 10.1038/NATURE12820
23 Jan 2014-Nature
Abstract: Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, 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, 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. 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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Topics: Microbiome (58%), Enterotype (55%), Gastrointestinal Microbiome (53%) ... show more

5,438 Citations


Journal ArticleDOI: 10.1038/NATURE05482
14 Dec 2006-Nature
Abstract: Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin - failure to control blood glucose levels results Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention

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Topics: Insulin resistance (75%), Insulin (66%), Type 2 diabetes (65%) ... show more

3,963 Citations


Journal ArticleDOI: 10.1038/NATURE11450
Junjie Qin, Yingrui Li, Zhiming Cai1, Shenghui Li  +53 moreInstitutions (8)
04 Oct 2012-Nature
Abstract: 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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Topics: Gut flora (56%), Microbial DNA (53%), Enterotype (53%) ... show more

3,910 Citations


Open accessJournal ArticleDOI: 10.2337/DIACARE.27.6.1487
01 Jun 2004-Diabetes Care
Abstract: Homeostatic model assessment (HOMA) is a method for assessing beta-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. It has been reported in >500 publications, 20 times more frequently for the estimation of IR than beta-cell function. This article summarizes the physiological basis of HOMA, a structural model of steady-state insulin and glucose domains, constructed from physiological dose responses of glucose uptake and insulin production. Hepatic and peripheral glucose efflux and uptake were modeled to be dependent on plasma glucose and insulin concentrations. Decreases in beta-cell function were modeled by changing the beta-cell response to plasma glucose concentrations. The original HOMA model was described in 1985 with a formula for approximate estimation. The computer model is available but has not been as widely used as the approximation formulae. HOMA has been validated against a variety of physiological methods. We review the use and reporting of HOMA in the literature and give guidance on its appropriate use (e.g., cohort and epidemiological studies) and inappropriate use (e.g., measuring beta-cell function in isolation). The HOMA model compares favorably with other models and has the advantage of requiring only a single plasma sample assayed for insulin and glucose. In conclusion, the HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data. However, as with all models, the primary input data need to be robust, and the data need to be interpreted carefully.

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Topics: Homeostatic model assessment (61%), Insulin resistance (59%), Insulin (51%) ... show more

3,854 Citations


Open accessJournal ArticleDOI: 10.1073/PNAS.1005963107
Abstract: Gut microbial composition depends on different dietary habits just as health depends on microbial metabolism, but the association of microbiota with different diets in human populations has not yet been shown. In this work, we compared the fecal microbiota of European children (EU) and that of children from a rural African village of Burkina Faso (BF), where the diet, high in fiber content, is similar to that of early human settlements at the time of the birth of agriculture. By using high-throughput 16S rDNA sequencing and biochemical analyses, we found significant differences in gut microbiota between the two groups. BF children showed a significant enrichment in Bacteroidetes and depletion in Firmicutes (P < 0.001), with a unique abundance of bacteria from the genus Prevotella and Xylanibacter, known to contain a set of bacterial genes for cellulose and xylan hydrolysis, completely lacking in the EU children. In addition, we found significantly more short-chain fatty acids (P < 0.001) in BF than in EU children. Also, Enterobacteriaceae (Shigella and Escherichia) were significantly underrepresented in BF than in EU children (P < 0.05). We hypothesize that gut microbiota coevolved with the polysaccharide-rich diet of BF individuals, allowing them to maximize energy intake from fibers while also protecting them from inflammations and noninfectious colonic diseases. This study investigates and compares human intestinal microbiota from children characterized by a modern western diet and a rural diet, indicating the importance of preserving this treasure of microbial diversity from ancient rural communities worldwide.

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Topics: Gut flora (57%), Enterotype (51%)

3,572 Citations


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