scholarly journals MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

2015 ◽  
Vol 172 (4) ◽  
pp. R167-R177 ◽  
Author(s):  
Kristine H Allin ◽  
Trine Nielsen ◽  
Oluf Pedersen

Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gut microbiota in the pathophysiology and pathogenesis of type 2 diabetes.

2021 ◽  
Vol 27 ◽  
Author(s):  
Daniela Sayuri Inoue ◽  
Mohammad Fauzan Bin Maideen ◽  
Alberto Jiménez-Maldonado ◽  
Fábio Santos Lira

: Obesity is associated with an exacerbated synthesis and secretion of several molecules, which culminates in chronic low-grade inflammation and insulin resistance. Such conditions affect molecular and physiological responses of several organs and, if not resolved, predispose to the obese patients to suffer other diseases such as Type 2 diabetes, atherosclerosis, cancer, neural injuries, and cognitive impairments. A microenvironment with an excess of pro-inflammatory cytokines released by different cells, including immune and adipose cells lead to suffer metabolic and non-metabolic diseases during obesity. In this context, the role of neuronal guidance cues named netrin, semaphorin and ephrin is novel. Specifically, the available literature indicates that besides to their classic role as molecules that guide to the axon with its target site, the neuronal guidance cues exhibit immunomodulatory functions from adipose tissue to the neural environment. In the current narrative review, we discuss the participation of the neuronal guidance cues on the physiology and pathophysiology of obesity. We also discuss the feedback loop of the obesity on the netrin, semaphorin and ephrin functions that impair the structure and function of the brain. The integrative view of the neuronal guidance cues can be relevant to design new treatments focused to attenuate metabolic and immune disorders that suffering obese patients, and lead to them to acquire worse diseases such as Type 2 diabetes, atherosclerosis, cancer, and neural injuries.


2021 ◽  
Vol 28 ◽  
Author(s):  
Lina Yang ◽  
Li Li ◽  
Xinghui Wu ◽  
Wenqi Cai ◽  
Qian Lin ◽  
...  

: Diabetes strongly influences patient quality of life. The incidence of type 2 diabetes (T2D) accounts for approximately 90% of diabetic patients. Natural polysaccharides have been widely used for diabetes management. Changes in gut microbiota can also be used for the prevention and treatment of diabetes. In this review, the effects of different natural polysaccharides on gut microbiota, as well as the relationship between diabetes and the gut microbiome are summarized. The intestine is the primary location in which natural polysaccharides exert their biological activities, and plays an important role in maintaining healthy bodily functions. Polysaccharides change the composition of the gut microbiota, which inhibits pathogen invasion and promotes beneficial bacterial growth. In addition, the gut microbiota degrade polysaccharides and produce metabolites to further modify the intestinal environment. Interestingly, the metabolites (short chain fatty acids and other bioactive components) have been shown to improve gut health, control glycemia, lower lipids, reduce insulin resistance, and alleviate inflammation. Therefore, understanding the underlying mechanisms by which soluble polysaccharides improve T2D through regulating the gut microbiota to provide a future reference for the management of T2D and its associated complications.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lili Zhang ◽  
Jinjin Chu ◽  
Wenhao Hao ◽  
Jiaojiao Zhang ◽  
Haibo Li ◽  
...  

Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.


2021 ◽  
Vol 12 ◽  
Author(s):  
M. Nazmul Huda ◽  
Myungsuk Kim ◽  
Brian J. Bennett

Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.


2021 ◽  
Author(s):  
Beate Vestad ◽  
Tuula Anneli Nyman ◽  
Malene Hove-Skovsgaard ◽  
Maria Stensland ◽  
Hedda Hoel ◽  
...  

Abstract Background: HIV and type 2 diabetes (T2D) are both associated with gut microbiota alterations, low-grade endotoxemia and increased cardiovascular risk. We investigated the potential role of plasma extracellular vesicles (EVs) in relation to these processes. Materials and methods: Plasma EVs were isolated by size exclusion chromatography in fasting individuals with HIV and T2D (n=16), T2D only (n=14), HIV only (n=20) or healthy controls (n=19), and characterized by transmission electron microscopy, western blot, nanoparticle tracking analysis and quantitative proteomics. The findings were compared to gut microbiota alterations, lipopolysaccharide levels and cardiovascular risk profile. Results: Individuals with concomitant HIV and T2D had higher plasma EV concentration, which correlated closely with plasma lipopolysaccharides, triglycerides and Framingham score, but not with gut microbiota alterations. Proteomic analyses identified 558 human proteins, largely related to cardiometabolic disease genes and upstream regulation of inflammatory pathways, including IL-6 and IL-1β, as well as 30 bacterial proteins, mostly from lipopolysaccharide-producing Proteobacteria. Conclusions: Our study supports that EVs are related to microbial translocation processes in individuals with HIV and T2D. Their proteomic content suggests a contributing role in low-grade inflammation and cardiovascular risk development. The present approach for exploring gut-host crosstalk can potentially identify novel diagnostic biomarkers and therapeutic targets.


2017 ◽  
Vol 71 (Suppl. 1) ◽  
pp. 17-22 ◽  
Author(s):  
Junko Sato ◽  
Akio Kanazawa ◽  
Hirotaka Watada

Background: A high proportion of type 2 diabetes cases are associated with host genetic and environmental factors. During the past decade, microorganisms that inhabit the gut have emerged as contributors to the pathogenesis of obesity and type 2 diabetes. Therefore, manipulation of the human gut microbiota will provide essential clues regarding new therapeutic targets for diabetes. Summary: Several studies have established the presence of gut dysbiosis in patients with type 2 diabetes mellitus, even though there are some differences among the studies that could be explained by differences in ethnicity, diet, and methodology. Gut dysbiosis affects the quality and quantity of short-chain fatty acids and secondary bile acids that act as signaling molecules in energy, glucose, and lipid metabolism. In addition, gut dysbiosis affect intestinal permeability. In particular, a high-fat diet can lead to changes in the gut microbiota that strongly reduce intestinal permeability due to the malfunction of tight junction proteins, such as occludin and ZO-1 [<citeref rid="ref1">1</citeref>]. The formation of leaky gut results in increased plasma levels of lipopolysaccharide, which activate Toll-like receptor 4 and result in innate and adaptive immune responses [<citeref rid="ref2">2</citeref>]. Key messages: Gut dysbiosis play an important role in the pathogenesis of obesity and diabetes, for example, via chronic low-grade inflammation. Normalizing gut dysbiosis could be a new approach to overcome diseases of insulin resistance, such as diabetes mellitus.


2016 ◽  
Vol 57 (3) ◽  
pp. 77-90
Author(s):  
V. M. Pushkarev ◽  
L. K. Sokolova ◽  
V. V. Pushkarev ◽  
M. D. Tronko

It was analyzed the cellular and molecular links between chronic low-grade inflammation and caused by inflammation insulin resistance and type 2 diabetes. Particular emphasis is placed on the participation of AMPK and mTORC1 in the development of metabolic diseases caused by obesity. A detailed analysis of the biochemical mechanisms of action of the main drug used in the treatment of insulin resistance and type 2 diabetes — metformin.


Author(s):  
Dominic Salamone ◽  
Angela Albarosa Rivellese ◽  
Claudia Vetrani

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
A. L. Cunningham ◽  
J. W. Stephens ◽  
D. A. Harris

AbstractA strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
You Lv ◽  
Xue Zhao ◽  
Weiying Guo ◽  
Ying Gao ◽  
Shuo Yang ◽  
...  

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.


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