scholarly journals Faecal virome transplantation decrease symptoms of type-2-diabetes and obesity in a murine model

2019 ◽  
Author(s):  
Torben Sølbeck Rasmussen ◽  
Caroline M. Junker Mentzel ◽  
Witold Kot ◽  
Josué L. Castro-Mejía ◽  
Simone Zuffa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Glucose Tolerance ◽  
Gut Microbiota ◽  
List Type ◽  
Proof Of Concept ◽  
Viral Community ◽  
Plasma Metabolome ◽  
New Findings

ABSTRACTObjectiveDevelopment of obesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. As a proof-of-concept we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.DesignThe FVT consisted of viromes extracted from the caecal content of mice fed a low-fat (LF) diet for fourteen weeks. Male C57BL/6NTac mice were divided into five groups: LF (as control), high-fat diet (HF), HF+Ampicillin (Amp), HF+Amp+FVT and HF+FVT. At week six and seven of the study the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with ampicillin 24 h prior to first FVT treatment.ResultsSix weeks after first FVT the HF+FVT mice showed a significant decrease in weight gain compared to the HF group. Further, glucose tolerance was comparable between the lean LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome, and expression levels of genes involved in obesity and T2D development.ConclusionsTransfer of gut viral communities from mice with a lean phenotype into those with an obese phenotype reduce weight gain and normalise blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.Significance of this studyWhat is already known about this subject?Obesity and type-2-diabetes (T2D) are associated with gut microbiota (GM) dysbiosis.Faecal microbiota transplant from lean donors has previously shown potential in treating obesity and T2D.Patients suffering from recurrent Clostridium difficile infections (rCDI) have been cured with sterile filtered donor faeces (containing enteric viruses and no bacteria), here defined as faecal virome transplantation (FVT).What are the new findings?FVT from lean donors lead to decreased weight gain and normalised blood sugar tolerance in a diet-induced obesity (DIO) mouse model.FVT significantly changed the bacterial and viral GM component, as well as the plasma metabolome and the expression profiles of obesity and T2D associated genes.Initial treatment with ampicillin prior FVT seems to counteract the beneficial effects associated with FVT.How might it impact on clinical practice in the foreseeable future?We here show a proof-of-concept, providing a solid base for designing a clinical study of FVT targeting obesity and T2D in humans. This is further augmented by the increased safety related to FVT, since bacteria and other microorganisms are removed from the donor faeces, and therefore minimises the risk of disease transmission.These findings highlight the potential application of FVT treatment of various diseases related to GM dysbiosis and further support the vital role of the viral community in maintaining and shaping the GM.

Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model

Gut ◽  
2020 ◽  
Vol 69 (12) ◽  
pp. 2122-2130 ◽  
Author(s):  
Torben Sølbeck Rasmussen ◽  
Caroline Märta Junker Mentzel ◽  
Witold Kot ◽  
Josué Leonardo Castro-Mejía ◽  
Simone Zuffa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Glucose Tolerance ◽  
Proof Of Concept ◽  
Oral Gavage ◽  
Plasma Metabolome ◽  
Viral Communities ◽  
Diet Control ◽  
Diabetes And Obesity

ObjectiveDevelopment of obesity and type 2 diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. The antagonistic behaviour of phages has the potential to alter the GM. As a proof-of-concept, we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.DesignThe FVT consisted of viromes with distinct profiles extracted from the caecal content of mice from different vendors that were fed a low-fat (LF) diet for 14 weeks. Male C57BL/6NTac mice were divided into five groups: LF (as diet control), high-fat (HF) diet, HF+ampicillin (Amp), HF+Amp+FVT and HF+FVT. At weeks 6 and 7 of the study, the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with Amp 24 hours prior to first FVT treatment.ResultsSix weeks after first FVT, the HF+FVT mice showed a significant decrease in weight gain compared with the HF group. Further, glucose tolerance was comparable between the LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome and expression levels of genes associated with obesity and T2D development.ConclusionsTransfer of caecal viral communities from mice with a lean phenotype into mice with an obese phenotype led to reduced weight gain and normalised blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.

scholarly journals Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM)

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3719
Author(s):  
Daniela Maria Tanase ◽  
Evelina Maria Gosav ◽  
Ecaterina Neculae ◽  
Claudia Florida Costea ◽  
Manuela Ciocoiu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Microvascular Complications ◽  
Aromatic Amino Acids ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Inflammatory Status ◽  
New Findings

Type 2 diabetes mellitus (T2DM) remains one of the most problematic and economic consumer disorders worldwide, with growing prevalence and incidence. Over the last years, substantial research has highlighted the intricate relationship among gut microbiota, dysbiosis and metabolic syndromes development. Changes in the gut microbiome composition lead to an imbalanced gastrointestinal habitat which promotes abnormal production of metabolites, inflammatory status, glucose metabolism alteration and even insulin resistance (IR). Short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide, aromatic amino acids and their affiliated metabolites, contribute to T2DM via different metabolic and immunologic pathways. In this narrative review, we discuss the immunopathogenic mechanism behind gut dysbiosis, T2DM development and the major known diabetic microvascular complications (retinopathy, neuropathy and nephropathy), the beneficial use of pre- and pro-biotics and fecal microbiota transplantation in T2DM management and new findings and future perspectives in this field.

Galacto-oligosaccharides ameliorate dysbiotic Bifidobacteriaceae decline in Japanese patients with type 2 diabetes

2017 ◽  
Vol 8 (5) ◽  
pp. 705-716 ◽  
Author(s):  
M. Gonai ◽  
A. Shigehisa ◽  
I. Kigawa ◽  
K. Kurasaki ◽  
O. Chonan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Impaired Glucose Tolerance ◽  
Healthy Subjects ◽  
Metabolic Diseases ◽  
Healthy Individuals ◽  
Patients With Diabetes ◽  
Metabolic Endotoxemia

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.

scholarly journals Risk-stratified lifestyle intervention to prevent type 2 diabetes

2021 ◽  
Author(s):  
Andreas Fritsche ◽  
Robert Wagner ◽  
Martin Heni ◽  
Kostantinos Kantartzis ◽  
Jürgen Machann ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Risk ◽  
Glucose Tolerance ◽  
Lifestyle Intervention ◽  
Fat Content ◽  
Low Risk ◽  
Liver Fat ◽  
List Type ◽  
Liver Fat Content

AbstractBackgroundLifestyle intervention (LI) can successfully prevent type 2 diabetes, but response to LI strongly varies depending on risk subphenotypes. We tested if individuals with prediabetes and a high-risk phenotype benefit from an intensification of LI.Methods and findingsWe conducted a risk stratified multicenter randomized controlled intervention study over 12 months with additional 2 year follow up. In eight University Hospitals in Germany, 1105 individuals (female 59%, age 58±11 years, BMI 31.1±6.0 kg/m2 (mean±SD)) with impaired fasting glucose and/or impaired glucose tolerance were included between May 2012 and May 2016 in the study. Participants were stratified into 2 groups; a high- and low-risk phenotype, based on insulin secretion, insulin sensitivity and liver fat content. Low-risk individuals were randomly assigned to conventional LI or control (1:1), high-risk individuals to conventional or intensified LI (1:1), each over one year. Intensified LI included doubling of physical exercise and time of counselling. The primary endpoint was change in post-challenge glucose levels, assessed by frequently sampled oral glucose tolerance tests. Secondary endpoints included changes in liver fat content, assessed by magnetic resonance spectroscopy. A total of 908 (82%) participants completed the study after 12 months of LI. In high-risk individuals, the mean difference estimate between conventional and intensified LI in change in post-challenge glucose levels from baseline was −0.290 mmol/l [CI: −0.544;−0.036], p=0.025. Liver fat content was more reduced by intensified LI than by conventional LI (mean difference estimate: −1.34 percentage points [CI: −2.17;−0.50], p=0.002), and cardiovascular risk decreased stronger with intensified LI than with conventional LI (mean difference estimate −1.82 [CI: −3.13−0.50], p=0.007). In low-risk individuals, conventional LI was not superior to control in reducing postprandial glucose, liver fat or cardiovascular risk. During the total observation period of 3 years, high-risk participants with intensified LI had a higher probability to normalize glucose tolerance compared to conventional LI (p=0.003). The limitations of this study include a relative short duration of LI, a non-completer rate of 18% and an underrepresentation of low risk individuals.ConclusionsIn high-risk individuals with prediabetes it is possible to improve glycemic and cardiometabolic outcomes by intensification of the commonly recommended conventional LI. Our results show that individualized, risk-phenotype-based LI can be implemented for the prevention of diabetes.RegistrationNCT01947595Author summaryWhy Was This Study Done?Clinical trials in individuals with prediabetes have shown that the onset of type 2 diabetes can be delayed or prevented with lifestyle intervention.Among individuals with prediabetes, there is a large variability in the response to lifestyle intervention.It is unknown whether an intensification of intervention is able to improve the beneficial response.What Did the Researchers Do and Find?The present multicenter, risk stratified randomized and controlled intervention trial in 1105 German individuals with prediabetes prospectively confirms the existence of a high-risk prediabetes phenotypeThe intensification of lifestyle intervention in high-risk individuals improves the glycemic outcome after 1 year of lifestyle intervention, and additionally results in a higher frequency of regression to normal glucose tolerance after 3 years of follow up..Intensification of lifestyle intervention results in a larger reduction of liver fat content and stronger improves cardiometabolic outcomes in high-risk individuals.What Do These Findings Mean?Strategies for the prevention of type 2 diabetes should include risk stratification and individualised interventions.Our results highlight a dose-effect relationship for lifestyle intervention and suggest that “one size fits NOT all” in the field of diabetes prevention.It remains to be clarified whether low risk individuals benefit from lifestyle intervention, as there was a low number of individuals in this risk group in the current study.

scholarly journals Effects of Resveratrol in Goto-Kakizaki Rat, a Model of Type 2 Diabetes

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2488 ◽  
Author(s):  
Katarzyna Szkudelska ◽  
Marzanna Deniziak ◽  
Iwona Hertig ◽  
Tatiana Wojciechowicz ◽  
Marianna Tyczewska ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Pancreatic Islets ◽  
Lipid Accumulation ◽  
Therapeutic Potential ◽  
Gk Rats ◽  
New Findings

Resveratrol exhibits a pleiotropic, favorable action under various pathological conditions, including type 2 diabetes. However, its anti-diabetic effects in animal models and human trials have not been fully elucidated. The aim of the present study was to determine whether resveratrol is capable of inducing beneficial changes in the Goto-Kakizaki rat, a spontaneous model of diabetes, which in several aspects is similar to type 2 diabetes in humans. Goto-Kakizaki (GK) rats and control Sprague–Dawley (SD) rats were treated intragastrically with resveratrol (20 mg/kg b.w./day) for 10 weeks. Then, a glucose tolerance test was performed and levels of some adipokines in blood were measured. Moreover, lipid contents in skeletal muscle and liver tissues, along with the expression and phosphorylation of pivotal enzymes (AMP—activated protein kinase—AMPK, acetyl-CoA carboxylase—ACC, protein kinase B—Akt) in these tissues were determined. Histology of pancreatic islets was also compared. GK rats non-treated with resveratrol displayed a marked glucose intolerance and had increased lipid accumulation in the skeletal muscle. Moreover, upregulation of the expression and phosphorylation of AMPK, ACC and Akt was shown in the muscle tissue of GK rats. Those rats also had an abnormal structure of pancreatic islets compared with control animals. However, treatment with resveratrol improved glucose tolerance and prevented lipid accumulation in the skeletal muscle of GK rats. This effect was associated with a substantial normalization of expression and phosphorylation of ACC and Akt. In GK rats subjected to resveratrol therapy, the structure of pancreatic islets was also clearly improved. Moreover, blood adiponectin and leptin levels were partially normalized by resveratrol in GK rats. It was revealed that resveratrol ameliorates key symptoms of diabetes in GK rats. This compound improved glucose tolerance, which was largely linked to beneficial changes in skeletal muscle. Resveratrol also positively affected pancreatic islets. Our new findings show that resveratrol has therapeutic potential in GK rats.

scholarly journals Evaluation of Poorly-Bioavailable Cocoa Flavanols and Their Gut Microbial Metabolites in Potentiating Anti-diabetic Activities Through BTBR.Cg-Lepob/ob/WiscJ Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 361-361
Author(s):  
Kathryn Racine ◽  
Lisard Iglesias-Carres ◽  
Lauren Essenmacher ◽  
Gabriella Agnello ◽  
Jeffery Tessem ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Gut Microbiota ◽  
Significant Protection ◽  
Peripheral Tissues ◽  
Progressive Type ◽  
Males And Females ◽  
The Impact ◽  
Cocoa Flavanols

Abstract Objectives Cocoa (Theobroma cacao) is a concentrated dietary source of flavanols that have beneficial activities against type-2 diabetes. These compounds have limited small intestinal absorption and are metabolized by the microbiota to bioavailable metabolites that may exert anti-diabetic effects locally and in peripheral tissues. Our objectives were to 1) determine the role of the gut microbiome in facilitating protective effects of cocoa flavanols, and 2) evaluate these effects in a novel mouse model of progressive type-2 diabetes. Methods A small pilot study (n = 3) of male and female BTBR mice (wild-type and homozygous for the Lepob mutation) received either control or cocoa extract-supplemented diet for 10 weeks. Half the animals were administered antibiotics orally to knock down the commensal gut microbiota. Glucose and insulin tolerance tests were conducted at weeks 1 and 5 and 2 and 6, respectively. Weight gain and food intake were monitored weekly. Biomarkers of gut integrity and inflammation were assessed by ELISA. Results Baseline fasting blood glucose (FBG) levels in five-week-old homozygous males and females were measured at 211–271 mg/dL and 112–234 mg/dL, respectively. After five weeks, FBG measured at 281–438 mg/dL and 177–562 mg/dL, respectively. Cocoa provided moderate, yet not significant, protection against weight gain in homozygous males when compared to homozygous males fed control diet. Cocoa provided no significant protection against hypoglycemia in homozygous male or female mice when compared to homozygous controls. In treatment comparisons with and without antibiotics, knocking out the commensal gut microbiota appeared to have minimal effect on weight gain and glycemic control in both males and females. Conclusions Cocoa did provide a moderate level of protection for homozygous males when directly comparing weight gain and FBG across sex. While the microbiome has displayed a promising role in the bioavailability of large flavanols, in this particular model, the impact was minimal. Overall, cocoa was ineffective against the mediation of advanced diabetes and further work must be conducted to understand if this conclusion is isolated to this model of progressive type-2 diabetes. Funding Sources This work was supported by the US Department of Agriculture by AFRI grant 2020–67,017-30,846.

scholarly journals Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation

2020 ◽  
Vol 318 (1) ◽  
pp. E52-E61
Author(s):  
Na Rae Shin ◽  
Namyi Gu ◽  
Han Seok Choi ◽  
Hojun Kim
Keyword(s):  
Type 2 Diabetes ◽  
Placebo Group ◽  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Metabolic Diseases ◽  
Scutellaria Baicalensis ◽  
Rrna Gene ◽  
Microbiota Composition

Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D.

scholarly journals Impact of altering gut microbiota metabolism on osteomyelitis severity in obesity-related type 2 diabetes

2022 ◽  
Author(s):  
Tina I Bui ◽  
Ann Lindley Gill ◽  
Robert A Mooney ◽  
Steven R Gill
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
High Fiber ◽  
Beneficial Effects ◽  
Plasma Metabolome ◽  
Hematogenous Seeding ◽  
Host Infection

Staphylococcus aureus is an opportunistic pathogen causing osteomyelitis through hematogenous seeding or contamination of implants and open wounds following orthopedic surgeries. The severity of S. aureus-mediated osteomyelitis is enhanced in obesity-related type 2 diabetes (obesity/T2D) due to chronic inflammation impairing both adaptive and innate immunity. Obesity-induced inflammation is linked to gut dysbiosis, with modification of the gut microbiota by high-fiber diets leading to a reduction in the symptoms and complications of obesity/T2D. However, our understanding of the mechanisms by which modifications of the gut microbiota alter host infection responses is limited. To address this gap, we monitored tibial S. aureus infections in obese/T2D mice treated with the inulin-like fructan fiber, oligofructose. Treatment with oligofructose significantly decreased S. aureus colonization and lowered proinflammatory signaling post-infection in obese/T2D mice, as observed by decreased circulating inflammatory cytokines (TNF-α) and chemokines (IP-10, KC, MIG, MCP-1, and RANTES), indicating partial reduction in inflammation. Oligofructose markedly shifted diversity in the gut microbiota of obese/T2D mice mice, with notable increases in the anti-inflammatory bacterium, Bifidobacterium pseudolongum. Analysis of the cecum and plasma metabolome suggested polyamine production was increased, specifically spermine and spermidine. Oral administration of these polyamines to obese/T2D mice resulted in reduced infection severity similar to oligofructose supplementation, suggesting polyamines can mediate the beneficial effects of fiber on osteomyelitis severity. These results demonstrate the contribution of gut microbiota metabolites to the control of bacterial infections distal to the gut and polyamines as an adjunct therapeutic for osteomyelitis in obesity/T2D.

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