scholarly journals Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Groot ◽  
Y.J Van De Vegte ◽  
N Verweij ◽  
E Lipsic ◽  
J.C Karper ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Gut Microbiome ◽  
Genetic Determinants ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Disease Outcomes ◽  
Health And Disease

Abstract Background Recent small-scale studies have suggested a link between the human gut microbiome and highly prevalent diseases. However, the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging has not been well established. In this study, we aimed to determine the spectrum of diseases that are linked to the human gut microbiome through the utilization of its genetic determinants as a proxy for its composition. Methods Data from 422,417 unrelated individuals of Caucasian British ancestry with available genotype and matching genetic data from the UK biobank was analysed in this study. 35 single nucleotide polymorphisms (SNPs) known to influence the human gut microbiome were used to perform the phenome-wide association study. Our main outcome was the probability (risk) of health and disease outcomes associated with human genetic determinants of the microbiome. Results From the total sample analysed (mean age was 57±8 years), 194,567 (46%) subjects were male. Median exposure was 66-person years (interquartile range 59 to 72). Seven SNPs known to influence the human gut microbiome were significantly associated with 29 health and disease outcomes (false discovery rate <5%, P value <9.14×10–4) including food intake, health status parameters (inflammation, blood pressure and lipid levels), hypertension, type 2 diabetes mellitus, hypercholesterolemia, heart failure, renal failure, and osteoarthritis. Conclusions Human genetic determinants of the gut microbiome are associated with 29 specific health and disease outcomes including hypertension, type 2 diabetes mellitus, hypercholesterolemia, heart failure, renal failure, and osteoarthritis. Microbiota and their metabolites play an important role in the interplay between overlapping pathophysiological processes and could be considered as potential targets for the maintenance of health and reduction of disease risk. Heat map Funding Acknowledgement Type of funding source: None

scholarly journals Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hilde E. Groot ◽  
Yordi J. van de Vegte ◽  
Niek Verweij ◽  
Erik Lipsic ◽  
Jacco C. Karper ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Healthy Aging ◽  
Total Sample ◽  
Causal Link ◽  
Small Scale ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Health And Disease

Abstract Small-scale studies have suggested a link between the human gut microbiome and highly prevalent diseases. However, the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown. We aimed to determine the spectrum of diseases that are linked to the human gut microbiome through the utilization of its genetic determinants as a proxy for its composition. 180 single nucleotide polymorphisms (SNPs) known to influence the human gut microbiome were used to assess the association with health and disease outcomes in 422,417 UK Biobank participants. Potential causal estimates were obtained using a Mendelian randomization (MR) approach. From the total sample analysed (mean age was 57 ± 8 years), 194,567 (46%) subjects were male. Median exposure was 66-person years (interquartile range 59–72). Eleven SNPs were significantly associated with 28 outcomes (Bonferroni corrected P value < 4.63·10−6) including food intake, hypertension, atopy, COPD, BMI, and lipids. Multiple SNP MR pointed to a possible causal link between Ruminococcus flavefaciens and hypertension, and Clostridium and platelet count. Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, although challenges remain in establishing causal relationships.

scholarly journals A neural network-based framework to understand the Type 2 Diabetes (T2D)-related alteration of the human gut microbiome

2020 ◽  
Author(s):  
Shun Guo ◽  
Haoran Zhang ◽  
Yunmeng Chu ◽  
Qingshan Jiang ◽  
Yingfei Ma
Keyword(s):  
Neural Network ◽  
Type 2 Diabetes ◽  
Gut Microbiome ◽  
Fasting Blood Glucose ◽  
Cumulative Effect ◽  
Marker Genes ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
And Control

ABSTRACTTo identify the microbial markers from the complex human gut microbiome for delineating the disease-related microbial alteration is of great interest. Here, we develop a framework combining neural network (NN) and random forest (RF), resulting in 40 marker species and 90 marker genes identified from the metagenomic dataset D1 (185 healthy and 183 type 2 diabetes (T2D) samples), respectively. Using these markers, the NN model obtains higher accuracy in classifying the T2D-related samples than machine learning-based approaches. The NN-based regression analysis determines the fasting blood glucose (FBG) is the most significant association factor (P<<0.05) in the T2D-related alteration of the gut microbiome. Twenty-four marker species that vary little across the case and control samples and are often neglected by the statistic-based methods greatly shift in different stages of the T2D development, implying that the cumulative effect of the markers rather than individuals likely drives the alteration of the gut microbiome.

scholarly journals Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes

2016 ◽  
Vol 23 (1) ◽  
pp. 10-12 ◽  
Author(s):  
Adil Mardinoglu ◽  
Jan Boren ◽  
Ulf Smith
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiome ◽  
Human Gut ◽  
Human Gut Microbiome

Abstract # P-15: Incremental Burden of Type 2 Diabetes Mellitus in Patients Hospitalized for Heart Failure

2016 ◽  
Vol 22 ◽  
pp. 20-21
Author(s):  
Aditya D. Raju ◽  
Anna D. Coutinho ◽  
Weijia Wang ◽  
Sharash Shetty ◽  
Stephen S. Sander ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus

1142-P: Comparison of Hospitalization for Heart Failure (HHF) among Patients with Type 2 Diabetes Mellitus (T2DM) and Macroalbuminuria Initiated on Canagliflozin (CANA) or a DPP-4

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1142-P
Author(s):  
DOMINIC PILON ◽  
MICHAEL DURKIN ◽  
AMEUR MANCEUR ◽  
ISABELLE GHELERTER ◽  
MARIE-HÉL LAFEUILLE ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

scholarly journals The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Potential Target ◽  
The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

GDF-15 and neutrophils in patients with heart failure and type 2 diabetes mellitus

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
AA Garganeeva ◽  
EA Kuzheleva ◽  
VA Fedyunina ◽  
VA Aleksandrenko
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Inflammatory Marker ◽  
Study Groups ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
National Budget

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was funded by (subject of fundamental scientific research on a state assignment № АААА-А17-117052310073-6 от 23.05.2017 Introduction. Growth differentiation factor-15 (GDF-15) is a biomarker associated with inflammatory processes in the pathogenesis of chronic heart failure (CHF) which expresses in cardiomyocytes under pathological conditions. The relationship between the level of GDF-15 and type 2 diabetes mellitus (T2DM) has also been proven. It is necessary to study GDF-15 in patients with CHF and T2DM. Aim To investigate the association between serum GDF-15 levels in patients with CHF of ischemic etiology and the concentration of the main leukocyte fractions depending on presence or absence of T2DM. Material and methods. The study included 42 patients. The patients were divided into 2 groups. The first group consisted of patients with CHF and T2DM (n = 14). The second group  consisted of patients with CHF without T2DM (n = 28). Determination of GDF-15 concentration was carried out by enzyme-linked immunosorbent assay (BioVendor, Czech Republic). The absolute concentration of lymphocytes, neutrophils, as well as the ratio of neutrophils to lymphocytes in the blood were analyzed. Statistical analysis was performed using the Statistica software (v.10.0). The data were described as a median and interquartile range, the Mann-Whitney test was used to compare them. The correlation analysis was tested using the Spearman"s correlation coefficient. Results and discussion. The average level of the GDF-15 in the study groups was comparable: 2389 (2104; 3375) pg/ml and 2309 (2047; 3014) pg/ml in the first and second groups, respectively (p = 0.6). In the general cohort of CHF patients, the GDF-15 concentration was not correlate with the lymphocytes concentration (r = -0.001, p = 0.95), neutrophils (r = -0.14, p = 0.4) and the ratio of neutrophils to lymphocytes (r = -0.12, p = 0.25). At the same time, in the group of patients with T2DM, a significant negative correlation was revealed between the concentration of GDF-15 in the serum and the concentration of neutrophils (r = -0.6, p = 0.022). While both other analyzed parameters did not demonstrate significant correlations with GDF-15 (p &gt; 0.05). In the group of CHF patients without T2DM, no correlations were found between GDF-15 and the studied parameters, including neutrophils (r = 0.02, p = 0.3). Along with this the median of the neutrophils concentration did not vary among groups (3.5 (2.3; 5.3) vs 3.2 (2.7; 4.1) * 109 / l; p = 0.8). Conclusion The concentration of the inflammatory marker GDF-15 in the blood of patients with CHF in combination with T2DM correlates with the concentration of neutrophils. In the absence of T2DM, no significant correlations were found between GDF-15 and the main leukocyte fractions. The results obtained indicate the possible prospect of using the GDF-15 biomarker in a cohort of patients with CHF in combination with T2DM.

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