Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.

/pdf/conserved-shifts-in-the-gut-microbiota-due-to-gastric-bypass-32i3genqkl.pdf

Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity

Roux-en-Y gastric bypass (RYGB) has become a prominent therapeutic option for long-term treatment of morbid obesity and type 2 diabetes mellitus (T2D). Cross talk and pathogenetic consequences of RYGB-induced profound effects on metabolism and gut microbiome are poorly understood. The aim of the present study therefore was to characterize intra-individual changes of gut microbial composition before and 3 months after RYGB by metagenomic sequencing in morbidly obese patients (body mass index (BMI)>40 kg m−2) with T2D. Subsequently, metagenomic data were correlated with clinical indices. Based on gene relative abundance profile, 1061 species, 729 genera, 44 phyla and 5127 KO (KEGG Orthology) were identified. Despite high diversity, bacteria could mostly be assigned to seven bacterial divisions. The overall metagenomic RYGB-induced shift was characterized by a reduction of Firmicutes and Bacteroidetes and an increase of Proteobacteria. Twenty-two microbial species and 11 genera were significantly altered by RYGB. Using principal component analysis, highly correlated species were assembled into two common components. Component 1 consisted of species that were mainly associated with BMI and C-reactive protein. This component was characterized by increased numbers of Proteobacterium Enterobacter cancerogenus and decreased Firmicutes Faecalibacterium prausnitzii and Coprococcus comes. Functional analysis of carbohydrate metabolism by KO revealed significant effects in 13 KOs assigned to phosphotransferase system. Spearmen’s Rank correlation indicated an association of 10 species with plasma total- or low-density lipoprotein cholesterol, and 5 species with triglycerides. F. prausnitzii was directly correlated to fasting blood glucose. This is the first clinical demonstration of a profound and specific intra-individual modification of gut microbial composition by full metagenomic sequencing. A clear correlation exists of microbiome composition and gene function with an improvement in metabolic and inflammatory parameters. This will allow to develop new diagnostic and therapeutic strategies based on metagenomic sequencing of the human gut microbiome.

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

Our aim was to study the potential mechanisms responsible for the improvement in glucose control in Type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Thirteen obese subjects ...

Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance

The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention. The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes. Dr. Barbara E. Corkey received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 71st Scientific Sessions, 24-28 June 2011, San Diego, California. She presented the Banting Lecture, "Hyperinsulinemia: Cause or Consequence?" on Sunday, 26 June 2011.

https://diabetes.diabetesjournals.org/content/diabetes/61/1/4.full.pdf

Banting Lecture 2011: Hyperinsulinemia: Cause or Consequence?

We performed a meta-analysis of weight loss and remission of type 2 diabetes mellitus (T2DM) evaluated in randomized controlled trials (RCTs) and observational studies of bariatric surgery vs conventional medical therapy. English articles published through June 10, 2013 that compared bariatric surgery with conventional therapy and included T2DM endpoints with ≥12-month follow-up were systematically reviewed. Body mass index (BMI, in kilogram per square meter), glycated hemoglobin (HbA1C, in degree), and fasting plasma glucose (FPG, in milligram per deciliter) were analyzed by calculating weighted mean differences (WMDs) and pooled standardized mean differences and associated 95 % confidence intervals (95 % CI). Aggregated T2DM remission event data were analyzed by calculating the pooled odds ratio (POR) and 95 % CI. Random effects assumptions were applied throughout; I
 2 ≥ 75.0 % was considered indicative of significant heterogeneity. Systematic review identified 512 articles: 47 duplicates were removed, 446 failed inclusion criteria (i.e., n < 10 per arm, animal studies, reviews, case reports, abstracts, and kin studies). Of 19 eligible articles, two not focused on diagnosed T2DM and one with insufficient T2DM data were excluded. In the final 16 included papers, 3,076 patients (mean BMI, 40.9; age, 47.0; 72.0 % female) underwent bariatric surgery; 3,055 (39.4; 48.6, 69.0 %) received conventional or no weight-loss therapy. In bariatric surgery vs conventional therapy groups, the mean 17.3 ± 5.7 month BMI WMD was 8.3 (7.0, 9.6; p < 0.001; I
 2 = 91.8), HbA1C was 1.1 (0.6, 1.6; p < 0.001; I
 2 = 91.9), and FPG, 24.9 (15.9, 33.9; p < 0.001; I
 2 = 84.8), with significant differences favoring surgery. The overall T2DM remission rate for surgery vs conventional group was 63.5 vs 15.6 % (p < 0.001). The Peto summary POR was 9.8 (6.1, 15.9); inverse variance summary POR was 15.8 (7.9, 31.4). Of the included studies, 94.0 % demonstrated a significant statistical advantage favoring surgery. In a meta-analysis of 16 studies (5 RCTs) with 6,131 patients and mean 17.3-month follow-up, bariatric surgery was significantly more effective than conventional medical therapy in achieving weight loss, HbA1C and FPG reduction, and diabetes remission. The odds of bariatric surgery patients reaching T2DM remission ranged from 9.8 to 15.8 times the odds of patients treated with conventional therapy.

/pdf/diabetes-and-weight-in-comparative-studies-of-bariatric-3kho1ozv1d.pdf

Diabetes and weight in comparative studies of bariatric surgery vs conventional medical therapy: a systematic review and meta-analysis.

Context: Roux-en-Y gastric bypass (RYGB) has been shown to induce rapid and durable reversal of type 2 diabetes. Objective: The aim of the study was to investigate a possible mechanism for the remission of type 2 diabetes after RYGB. Design: A cross-sectional, nonrandomized, controlled study was conducted. Surgery patients were studied before RYGB and 1 wk and 3 months after surgery. Setting: This study was conducted at East Carolina University. Subjects: Subjects were recruited into three groups: 1) lean controls with no surgery [body mass index (BMI) 35 kg/m2; n = 9), and 3) severely obese nondiabetic patients (BMI > 35 kg/m2; n = 9). Intervention: Intervention was RYGB. Results: One week after RYGB, diabetes was resolved despite continued insulin resistance (insulin sensitivity index was approximately 50% of lean controls) and reduced insulin secretion during an iv glucose tolerance test (acute insulin response to glucose was approxi...

Roux-en-Y gastric bypass corrects hyperinsulinemia implications for the remission of type 2 diabetes.

Department of Endocrinology-Metabolism, School of Medicine, Catholic University, Daegu, Korea Address correspondence to: G. Lynis Dohm, Ph.D. Department of Physiology Brody School of Medicine East Carolina University 6N98 600 Moye Blvd Greenville, NC 27834 Tel: (252) 744-2682 Fax: (252) 744-3460 E-mail: dohmg@ecu.edu Disclosure Statement: The authors have nothing to disclose. Keywords: Gastric Bypass, Insulin Sensitivity, Glucose Transport, BMI, IKKβSupport: This work was supported by NIH grant R01 DK046121 (to G.L.D.). Word count (text): 3,742 Word count (abstract): 236 Tables: 1 Figures: 9

MECHANISM FOR IMPROVED INSULIN SENSITIVITY AFTER GASTRIC BYPASS SURGERY Short Title: Gastric Bypass and Insulin Sensitivity

Context: Surgical treatments of obesity have been shown to induce rapid and prolonged improvements in insulin sensitivity. Objective: The aim of the study was to investigate the effects of gastric bypass surgery and the mechanisms that explain the improvement in insulin sensitivity. Design: We performed a cross-sectional, nonrandomized, controlled study. Setting: This study was conducted jointly between the Departments of Exercise Science and Physiology at East Carolina University in Greenville, North Carolina. Subjects: Subjects were recruited into four groups: 1) lean [body mass index (BMI) 35 kg/m2; n = 43); and 4) postsurgery patients (BMI ≈ 30 kg/m2; n = 40). Postsurgery patients were weight stable 1 yr after surgery. Main Outcome Measures: Whole-body insulin sensitivity, muscle glucose transport, and muscle insulin signaling were assessed. Results: Postsurgery subjects had insulin sensitivity index value...

/pdf/mechanism-for-improved-insulin-sensitivity-after-gastric-4rh0478jze.pdf

Mechanism for Improved Insulin Sensitivity after Gastric Bypass Surgery

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Roux-en-Y gastric bypass corrects hyperinsulinemia implications for the remission of type 2 diabetes.

MECHANISM FOR IMPROVED INSULIN SENSITIVITY AFTER GASTRIC BYPASS SURGERY Short Title: Gastric Bypass and Insulin Sensitivity

Mechanism for Improved Insulin Sensitivity after Gastric Bypass Surgery