scholarly journals Plasma extracellular vesicles in people living with HIV and type 2 diabetes are related to microbial translocation and cardiovascular risk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Beate Vestad ◽  
Tuula A. Nyman ◽  
Malene Hove-Skovsgaard ◽  
Maria Stensland ◽  
Hedda Hoel ◽  
...  

AbstractHIV 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. 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. 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. 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.

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.


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.


Gut Microbes ◽  
2012 ◽  
Vol 3 (4) ◽  
pp. 279-288 ◽  
Author(s):  
Patrice D. Cani ◽  
Melania Osto ◽  
Lucie Geurts ◽  
Amandine Everard

2016 ◽  
Vol 7 (2) ◽  
pp. 181-194 ◽  
Author(s):  
R. Nagpal ◽  
M. Kumar ◽  
A.K. Yadav ◽  
R. Hemalatha ◽  
H. Yadav ◽  
...  

In concern to the continuously rising global prevalence of obesity, diabetes and associated diseases, novel preventive and therapeutic approaches are urgently required. However, to explore and develop such innovative strategies, a meticulous comprehension of the biological basis of these diseases is extremely important. Past decade has witnessed an enormous amount of research investigation and advancement in the field of obesity, diabetes and metabolic syndrome, with the gut microbiota receiving a special focus in the triangle of nutrition, health and diseases. In particular, the role of gut microbiota in health and diseases has been one of the most vigorous and intriguing field of recent research; however, much still remains to be elucidated about its precise role in host metabolism and immune functions and its implication in the onset, progression as well as in the amelioration of metabolic ailments. Recent investigations have suggested a significant contribution of the gut microbiota in the regulation and impairment of energy homeostasis, thereby causing metabolic disorders, such as metabolic endotoxemia, insulin resistance and type 2 diabetes. Numerous inflammatory biomarkers have been found to be associated with obesity, diabetes and risk of other associated adverse outcomes, thereby suggesting that a persistent low-grade inflammatory response is a potential risk factor. In this milieu, this review intends to discuss potential evidences supporting the disturbance of the gut microbiota balance and the intestinal barrier permeability as a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.


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.


2019 ◽  
Vol 10 (4) ◽  
pp. 1915-1927 ◽  
Author(s):  
Ke Li ◽  
Li Zhang ◽  
Jing Xue ◽  
Xiaoli Yang ◽  
Xiaoying Dong ◽  
...  

Type 2 diabetes mellitus (T2DM) is closely correlated with chronic low-grade inflammation and gut dysbiosis.


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.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Marjo Tuomainen ◽  
Jaana Lindström ◽  
Marko Lehtonen ◽  
Seppo Auriola ◽  
Jussi Pihlajamäki ◽  
...  

Author(s):  
L. A. Kharitonova ◽  
O. V. Papisheva ◽  
T. A. Mayatskaya ◽  
G. A. Kotaysh

The gut microbiota has attracted increasing attention during the last several years as a key player in the pathophysiology of chronic disease. Microbiome is considered to be the link between metabolic disorders, obesity, insulin resistance, dyslipidemia, diabetes, hypertension and cardiovascular diseases. Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes, obesity, cholelithiasis and nonalcoholic steatohepatitis. This review presents potential mechanisms for the development of these diseases in response to changes in the gut microbiota. They involve increased gut permeability, low-grade inflammation and autoantibodies. Many studies contradict each other, which confirms the need for further scientific research in this area.


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