scholarly journals Gut microbiota and health: connecting actors across the metabolic system

2018 ◽  
Vol 78 (02) ◽  
pp. 177-188 ◽  
Author(s):  
F. Fava ◽  
L. Rizzetto ◽  
K. M. Tuohy

Overweight-related metabolic diseases are an important threat to health in the Western world. Dietary habits are one of the main causative factors for metabolic syndrome, CVD and type 2 diabetes. The human gut microbiota is emerging as an important player in the interaction between diet and metabolic health. Gut microbial communities contribute to human metabolism through fermentation of dietary fibre and the result of intestinal saccharolytic fermentation is production of SCFA. Acetate, propionate and butyrate positively influence satiety, endocrine system, glucose homeostasis, adipogenesis, lipid oxidation, thermoregulation, hepatic gluconeogenesis, endothelial function and gut barrier integrity, and these mechanisms have all been linked to protection from type 2 diabetes, hypertension and cardiovascular health. The gut microbiota is also involved in bile acid metabolism and regulating their cell signalling potential, which has also been shown to modify pathways involved in metabolic health. Similarly, the gut microbiota renders recalcitrant plant polyphenols into biologically active small phenolic compounds which then act systemically to reduce metabolic disease risk. This review summarises how dietary patterns, specific foods and a healthy lifestyle may modulate metabolic health through the gut microbiota and their molecular cross-talk with the host.

Toxics ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 54 ◽  
Author(s):  
Todd Leff ◽  
Paul Stemmer ◽  
Jannifer Tyrrell ◽  
Ruta Jog

Although the increased incidence of type 2 diabetes since the 1950s is thought to be primarily due to coincident alterations in lifestyle factors, another potential contributing factor in industrialized countries is exposure of the population to environmental pollutants and industrial chemicals. Exposure levels of many environmental toxicants have risen in the same time-frame as the disease incidence. Of particular interest in this regard is the metal lead. Although overall lead exposure levels have diminished in recent decades, there is an under-recognized but persistent occurrence of lead exposure in poor underserved urban populations. Although the neural developmental pathologies induced by lead exposures have been well documented, very little is known about the effect of lead exposure on the incidence of chronic metabolic diseases such as type 2 diabetes. Although our understanding of the metabolic health effects of lead exposure is incomplete, there are studies in model systems and a small amount of epidemiological data that together suggest a deleterious effect of environmental lead exposure on metabolic health. This article reviews the human, animal and in vitro studies that have examined the effects of lead exposure on the development of diabetes and related metabolic conditions.


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.


2017 ◽  
Vol 8 (5) ◽  
pp. 705-716 ◽  
Author(s):  
M. Gonai ◽  
A. Shigehisa ◽  
I. Kigawa ◽  
K. Kurasaki ◽  
O. Chonan ◽  
...  

Gut microbiota affects the host’s metabolism, and it is suggested that there are differences in gut microbiota composition between patients with type 2 diabetes and healthy individuals. Additionally, dysbiosis may increase the concentration of lipopolysaccharides (LPS), causing metabolic endotoxemia, which induces impaired glucose tolerance. Several studies have reported relationships between metabolic diseases and the gut microbiota; and prebiotics, such as oligosaccharides, are commonly consumed to regulate gut microbiotas in healthy individuals. Galacto-oligosaccharides (GOS) are a major prebiotic, which specifically increase Bifidobacteriaceae abundance. Recent studies have reported that Bifidobacteriaceae improved metabolic endotoxemia or impaired glucose tolerance. However, there are few studies reporting the effects of GOS on patients with type 2 diabetes. In the current study, we compared clinical parameters, faecal gut microbiota, their associated metabolic products and their components such as LPS, and LPS-binding protein (LBP) produced by the host, between patients with diabetes and healthy controls. We then assessed the effects of GOS on glycaemic control, and gut microbiotas and metabolites in patients with type 2 diabetes in a double-blind controlled manner. LBP levels were significantly higher in patients with diabetes than those of healthy subjects, which was consistent with previous reports. The abundance of Bifidobacteriaceae and the diversity of intestinal microbiota were significantly lower in patients with diabetes than in healthy subjects. Interestingly, Bifidobacteriaceae was markedly restored in patients with diabetes after consumption of GOS, whereas LBP and glucose tolerance did not improve during this short-term trial period. In the present study, we demonstrated that GOS can ameliorate dysbiosis in patients with diabetes, and continuous intake of GOS may be a promising method for managing type 2 diabetes.


Author(s):  
К. О. Shyshkan-Shyshova ◽  
O. V. Zinych

Recent advances in molecular and genetic research have illuminated the mechanisms of interaction between genes and the environment, which are partially mediated by so-called epigenetic modifications. These changes do not affect the primary structure of genes’ DNA, but cause persistent changes in their expression, which can be inherited by subsequent generations and determine the formation of the corresponding metabolic phenotype. Obesity, metabolic syndrome and type 2 diabetes mellitus develop on the basis of insulin resistance in the presence of a genetic predisposition under the influence of external factors, including environmental influences and lifestyle characteristics, in particular dietary habits. Today it has been proven that changes in the profile of intestinal microbiota is an important modifiable factor in the development of dysmetabolic states. Gut microbiota plays a key role in the regulation of many metabolic processes, inflammation, the activity of the immune system and the general state of the body. Diets enriched with fats and carbohydrates have been found to result in the decreased diversity and changes in gut microbiota composition, such as decreased levels of Bacteroidetes and increased Firmicutes. The accumulated data of clinical and experimental studies indicate a link between disorders in the composition and function of the intestinal microbiome (dysbiosis) and obesity, impaired glycemic control, and, consequently, the pathophysiology of type 2 diabetes. These induced epigenetic modifications are regulated by metabolites produced by the gut microbiota, such as short-chain fatty acids (acetate, propionate, butyrate), cysteine, mercaptans, which can influence epigenetic processes through their effects on DNA methylation, acetylation and histone modification. Moreover, the direct effects of the microbial environment on the secretion of incretins by intestinal enteroendocrine cells play an important role. The review discusses some of the mechanisms of epigenetic modifications through which the microbiota influences the development of obesity and type 2 diabetes mellitus.


2020 ◽  
Vol 15 (3) ◽  
pp. 177-183
Author(s):  
Anna Kotrova ◽  
◽  
Alexandr Shishkin ◽  
Maria Lukashenko ◽  
◽  
...  

Obesity, type 2 diabetes mellitus, metabolic syndrome are metabolic widespread disorders that arise both under the influence of external factors (physical inactivity, high-calorie diet) and under the influence of internal factors. The latter includes the intestinal microbiota which deserves more and more attention in developing new strategies for the correction of metabolic diseases. The discovery of new approaches for the gut microbiota study (metagenomic, metabolomic) gives a new insight into the diversity and involvement of intestinal bacteria in the metabolic processes of the whole organism. This article are reviewed the mechanisms of the gut bacteria impact on lipid and carbohydrate metabolism, the relationship of bacteria species and their metabolites with tissue insulin sensitivity, body mass index. Special attention in the regulation of tissue insulin sensitivity is paid to the role of short-chain fatty acids and secondary bile acids, which are metabolites of gut bacteria. Understanding the influence of human microbiota and its metabolites on lipid and carbohydrate metabolism provides the basis for the development of new approaches to the prevention and treatment of socially significant metabolic diseases such as type 2 diabetes mellitus, obesity, metabolic syndrome.


2014 ◽  
Vol 73 (2) ◽  
pp. 271-277 ◽  
Author(s):  
Patrick Schrauwen ◽  
Silvie Timmers

The number of people suffering from metabolic diseases is dramatically increasing worldwide. This stresses the need for new therapeutic strategies to combat this growing epidemic of metabolic diseases. A reduced mitochondrial function is one of the characteristics of metabolic diseases and therefore a target for intervention. Here we review the evidence that mitochondrial function may act as a target to treat and prevent type 2 diabetes mellitus, and, if so, whether these effects are due to reduction in skeletal muscle fat accumulation. We describe how exercise may affect these parameters and can be beneficial for type 2 diabetes. We next focus on alternative ways to improve mitochondrial function in a non-exercise manner. Thus, in 2003, resveratrol (3,5,4′-trihydroxystilbene) was discovered to be a small molecule activator of sirtuin 1, an important molecular target regulating cellular energy metabolism and mitochondrial homoeostasis. Rodent studies have clearly demonstrated the potential of resveratrol to improve various metabolic health parameters. Here we review data in human subjects that is available on the effects of resveratrol on metabolism and mitochondrial function and discuss how resveratrol may serve as a new therapeutic strategy to preserve metabolic health. We also discuss whether the effects of resveratrol are similar to the effects of exercise training and therefore if resveratrol can be considered as an exercise mimetic.


2021 ◽  
Vol 9 (3) ◽  
pp. 618
Author(s):  
Raluca Anca Corb Aron ◽  
Areha Abid ◽  
Cosmin Mihai Vesa ◽  
Aurelia Cristina Nechifor ◽  
Tapan Behl ◽  
...  

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are diseases that can be influenced by the structure of gut microbiota, whose improvement is often neglected in metabolic pathology. This review highlights the following main aspects: the relationship between probiotics/gut microbes with the pathogenesis of MetS, the particular positive roles of Akkermansia muciniphila supplementation in the onset of MetS, and the interaction between dietary polyphenols (prebiotics) with gut microbiota. Therefore, an extensive and in-depth analysis of the often-neglected correlation between gut microbiota and chronic metabolic diseases was conducted, considering that this topic continues to fascinate and stimulate researchers through the discovery of novel strains and their beneficial properties.


Author(s):  
Bhupendra Chaudhary ◽  
Ansh Chaudhary

The gut microbiota comprises of bacteria, viruses, protozoa and fungi living in different districts of human body with over 70% in gastrointestinal tract. They generally live in mutually beneficial relationships in gut. It has been proved that abnormalities in composition of microbiota are often associated with presence of common metabolic diseases, type 2 diabetes and lipid disorders. Recently gut microbiota are found to be major culprits in etiopathogenesis of various neuropsychiatric disorders which are triggered by stress induced down regulation of immune system of body. The association of gut microbiota with diseases like anxiety, depression, autism, bipolar disorder, Parkinson’s disease and multiple sclerosis has developed new insight in management of these diseases and advocates the need of further research in this area.


mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Xiaolin Tong ◽  
Jia Xu ◽  
Fengmei Lian ◽  
Xiaotong Yu ◽  
Yufeng Zhao ◽  
...  

ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp. IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota. Blautia spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of Faecalibacterium spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula.


2021 ◽  
Vol 22 (19) ◽  
pp. 10647
Author(s):  
Mark Agostino ◽  
Jennifer Rooney ◽  
Lakshini Herat ◽  
Jennifer Matthews ◽  
Allyson Simonds ◽  
...  

Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with glucose intolerance and insulin resistance, often culminating in Type 2 diabetes (T2D). Importantly, our team has recently shown that the TNF superfamily (TNFSF) member protein, TNFSF14, has been reported to protect against high fat diet induced obesity and pre-diabetes. We hypothesized that mimics of TNFSF14 may therefore be valuable as anti-diabetic agents. In this study, we use in silico approaches to identify key regions of TNFSF14 responsible for binding to the Herpes virus entry mediator and Lymphotoxin β receptor. In vitro evaluation of a selection of optimised peptides identified six potentially therapeutic TNFSF14 peptides. We report that these peptides increased insulin and fatty acid oxidation signalling in skeletal muscle cells. We then selected one of these promising peptides to determine the efficacy to promote metabolic benefits in vivo. Importantly, the TNFSF14 peptide 7 reduced high fat diet-induced glucose intolerance, insulin resistance and hyperinsulinemia in a mouse model of obesity. In addition, we highlight that the TNFSF14 peptide 7 resulted in a marked reduction in liver steatosis and a concomitant increase in phospho-AMPK signalling. We conclude that TNFSF14-derived molecules positively regulate glucose homeostasis and lipid metabolism and may therefore open a completely novel therapeutic pathway for treating obesity and T2D.


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