Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters

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

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

10.1101/2020.09.06.284885 ◽

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.

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

Cell Metabolism ◽

10.1016/j.cmet.2015.12.012 ◽

2016 ◽

Vol 23 (1) ◽

pp. 10-12 ◽

Cited By ~ 30

Author(s):

Adil Mardinoglu ◽

Jan Boren ◽

Ulf Smith

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome

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Bariatric surgery versus medical treatment in mildly obese patients with type 2 diabetes mellitus in Japan: propensity score‐matched analysis on real‐world data

Journal of Diabetes Investigation ◽

10.1111/jdi.13631 ◽

2021 ◽

Author(s):

Yosuke Seki ◽

Kazunori Kasama ◽

Renzo Yokoyama ◽

Akihiro Maki ◽

Hideharu Shimizu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Bariatric Surgery ◽

Type 2 Diabetes Mellitus ◽

Propensity Score ◽

Medical Treatment ◽

Real World ◽

Obese Patients ◽

Real World Data

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All obese patients with type 2 diabetes should be assessed for bariatric surgery, says NICE

BMJ ◽

10.1136/bmj.g7246 ◽

2014 ◽

Vol 349 (nov26 12) ◽

pp. g7246-g7246 ◽

Cited By ~ 1

Author(s):

J. Wise

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Obese Patients

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A Nationwide Safety Analysis of Bariatric Surgery In Nonmorbidly Obese Patients With Type 2 Diabetes

Surgery for Obesity and Related Diseases ◽

10.1016/j.soard.2015.10.027 ◽

2015 ◽

Vol 11 (6) ◽

pp. S18-S19

Author(s):

Ali Aminian ◽

John Kirwan ◽

Bartolome Burguera ◽

Stacy Brethauer ◽

Philip Schauer

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Safety Analysis ◽

Obese Patients

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Abstract 15004: Bariatric Surgery is Associated With Reduced Atherosclerotic Cardiovascular Disease Burden in Obese Patients With Type 2 Diabetes: A Propensity-matched Cohort Study

Circulation ◽

10.1161/circ.142.suppl_3.15004 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Francesca Watson ◽

Maddalena Ardissino ◽

Ravi J Amin ◽

Chanpreet Arhi ◽

Peter Collins ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Bariatric Surgery ◽

Disease Burden ◽

Atherosclerotic Cardiovascular Disease ◽

Obese Patients ◽

Matched Cohort ◽

All Cause Mortality

Introduction: Obesity is an increasingly prevalent global health issue and has a considerable disease burden, including numerous co-morbidities. Atherosclerotic cardiovascular disease (ASCVD) is one such co-morbidity associated with a high mortality rate and prevalence, especially in patients with obesity and concomitant Type 2 diabetes mellitus (T2DM). Bariatric surgery is an effective intervention for patients with obesity, shown to reduce overall cardiovascular disease risk. However, few studies have quantified the long-term impact of bariatric surgery on ASCVD outcomes in the context of key co-morbidities such as T2DM. Hypothesis: Bariatric surgery will improve long-term ASCVD outcomes in obese patients with T2DM. Methods: A nested, nationwide, propensity-matched cohort study was carried out using the Clinical Practice Research Datalink. The study cohort included 593 patients who underwent bariatric surgery and had no past history of ASCVD. A further 593 patients served as propensity-score matched controls. Patients were followed up for a median time of 47.2 months. The primary composite study endpoint was the incidence of ASCVD defined by a diagnosis of new coronary artery disease (CAD), cerebrovascular disease (CeVD), peripheral arterial disease (PAD), or other miscellaneous atherosclerotic disease. Secondary endpoints included all-cause mortality and the incidence of CAD, CeVD, and PAD individually. Results: Patients who underwent bariatric surgery had significantly lower rates of new ASCVD during follow-up (HR 0.53, CI 0.30-0.95, p=0.032). No significant difference was observed in rates of new CAD (HR 0.69, CI 0.32-1.46, p=0.331), CeVD (HR 0.23, CI 0.00-5.45, p=0.1760) and PAD (HR 0.55, CI 0.21-1.43, p=0.218). The bariatric surgery group also had a lower rate of all-cause mortality (HR 0.36, CI 0.19-0.71, p=0.003) compared to controls. Conclusions: In this study, bariatric surgery was associated with improved ASCVD outcomes, as well as lower all-cause mortality, in patients with obesity and T2DM. These findings support the use of bariatric surgery in treating obesity and reducing the burden of its related comorbidities.

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Cost-Effectiveness of Bariatric Surgery versus Medication Therapy for Obese Patients with Type 2 Diabetes in China: A Markov Analysis

Journal of Diabetes Research ◽

10.1155/2019/1341963 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Bin Wan ◽

Nan Fang ◽

Wei Guan ◽

Haixia Ding ◽

Ying Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Health Care ◽

Health Insurance ◽

Cost Effectiveness ◽

Time Horizon ◽

Obese Patients ◽

Medication Therapy ◽

Insurance Payer

Aims/Introduction. The present study estimated the cost-effectiveness of bariatric surgery versus medication therapy for the management of recently diagnosed type 2 diabetes mellitus (T2DM) in obese patients from a Chinese health insurance payer perspective. Materials and Methods. A Markov model was established to compare the 40-year time costs and quality-adjusted life-years (QALYs) between bariatric surgery and medication therapy. The health-care costs in the bariatric surgery group, proportion of patients in each group with remission of diabetes, and state transition probabilities were calculated based on observed resource utilization from the hospital information system (HIS). The corresponding costs in the medication therapy group were derived from the medical insurance database. QALYs were estimated from previous literature. Costs and outcomes were discounted 5% annually. Results. In the base case analysis, bariatric surgery was more effective and less costly than medication therapy. Over a 40-year time horizon, the mean discounted costs were 86,366.55 RMB per surgical therapy patient and 113,235.94 CNY per medication therapy patient. The surgical and medication therapy patients lived 13.46 and 10.95 discounted QALYs, respectively. Bariatric surgery was associated with a mean health-care savings of 26,869.39 CNY and 2.51 additional QALYs per patient compared to medication therapy. Uncertainty around the parameter values was tested comprehensively in sensitivity analyses, and the results were robust. Conclusions. Bariatric surgery is a dominant intervention over a 40-year time horizon, which leads to significant cost savings to the health insurance payer and increases in health benefits for the management of recently diagnosed T2DM in obese patients in China.

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