scholarly journals Longitudinal Multi-omic Phenotyping Reveals Host-microbe Responses to Bariatric Surgery, Glycaemic Control and Obesity

Author(s):  
Nicholas Penney ◽  
Derek Yeung ◽  
Isabel Garcia-Perez ◽  
Joram POSMA ◽  
Aleksandra Kopytek ◽  
...  

Abstract Resolution of type-2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). However, the underlying mechanisms have not been fully elucidated. To address this we compared the integrated serum, urine and faecal metabolic profiles of obese participants with and without T2D (n=81, T2D=42) with participants who underwent RYGB or sleeve gastrectomy (pre and 3-months post-surgery; n=27), taking diet into account. We co-modelled these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level. Bariatric surgery reversed a number of disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlapped with both diabetes (19.3% commonality) and BMI (18.6% commonality). However, the percentage overlap between diabetes and BMI was minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota was more strongly correlated to BMI than T2D, although we identified some pathways such as amino acid metabolism that correlated with changes to the gut microbiota and which influence glycaemic control. Improved understanding of GM-host co-metabolism may lead to novel therapies for weight-loss or diabetes.

Author(s):  
Michelle Maher ◽  
Mohammed Faraz Rafey ◽  
Helena Griffin ◽  
Katie Cunningham ◽  
Francis M Finucane

Summary A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team. Learning points: Meal replacement programmes are an emerging therapeutic strategy to allow severely obese type 2 diabetes patients to achieve clinically impactful weight loss. Using semi-skimmed milk as a meal replacement substrate might be less costly than commercially available programmes, but is likely to require intensive multidisciplinary bariatric clinical follow-up. For severely obese adults with poor diabetes control who decline bariatric surgery or GLP1 agonist therapy, a milk-based meal replacement programme may be an option. Milk-based meal replacement in patients with insulin requiring type 2 diabetes causes rapid and profound reductions in insulin requirements, so rigorous monitoring of glucose levels by patients and their clinicians is necessary. In carefully selected and adequately monitored patients, the response to oral antidiabetic medications may help to differentiate between absolute and relative insulin deficiency.


Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 721
Author(s):  
Tannaz Jamialahmadi ◽  
Mohsen Nematy ◽  
Simona Bo ◽  
Valentina Ponzo ◽  
Ali Jangjoo ◽  
...  

Background: Obesity is a chronic inflammatory condition associated with increased circulating levels of C-reactive protein (CRP). Bariatric surgery has been reported to be effective in improving both inflammatory and liver status. Our aims were to elucidate the relationships between pre-surgery high sensitivity-CRP (hs-CRP) values and post-surgery weight loss and liver steatosis and fibrosis in patients with severe obesity undergoing Roux-en-Y gastric bypass. Methods: We conducted an observational prospective study on 90 individuals with morbid obesity, who underwent gastric bypass. Anthropometric indices, laboratory assessment (lipid panel, glycemic status, liver enzymes, and hs-CRP), liver stiffness and steatosis were evaluated at baseline and 6-months after surgery. Results: There was a significant post-surgery reduction in all the anthropometric variables, with an average weight loss of 33.93 ± 11.79 kg; the mean percentage of total weight loss (TWL) was 27.96 ± 6.43%. Liver elasticity was significantly reduced (from 6.1 ± 1.25 to 5.42 ± 1.52 kPa; p = 0.002), as well as liver aminotransferases, nonalcoholic fatty liver disease fibrosis score (NFS) and the grade of steatosis. Serum hs-CRP levels significantly reduced (from 9.26 ± 8.45 to 3.29 ± 4.41 mg/L; p < 0.001). The correlations between hs-CRP levels and liver fibrosis (elastography), steatosis (ultrasonography), fibrosis-4 index, NFS, and surgery success rate were not significant. Regression analyses showed that serum hs-CRP levels were not predictive of liver status and success rate after surgery in both unadjusted and adjusted models. Conclusions: In patients with morbid obesity, bariatric surgery caused a significant decrease in hs-CRP levels, liver stiffness and steatosis. Baseline hs-CRP values did not predict the weight-loss success rate and post-surgery liver status.


2021 ◽  
Author(s):  
Yongli Zhang ◽  
Tao Wu ◽  
Wen Li ◽  
Yunjiao Zhao ◽  
Hairong Long ◽  
...  

Previous study suggests Lactobacillus casei exhibit antihyperglycemic activity, however, the molecular mechanism has rarely been elucidated. Here, the anti-diabetic effects and underlying mechanisms of Lactobacillus casei LC89 were investigated in...


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew Yang ◽  
Melinda Nguyen ◽  
Irene Ju ◽  
Anthony Brancatisano ◽  
Brendan Ryan ◽  
...  

AbstractSignificant weight loss can modify the progression of Nonalcoholic fatty liver disease (NAFLD) with the most convincing evidence coming from bariatric surgery cohorts. Effective ways to non-invasively characterise NAFLD in these patients has been lacking, with high Fibroscan failure rates reported. We prospectively evaluated the utility of Fibroscan using XL-probe over a two-year period. 190 consecutive patients undergoing bariatric surgery were followed as part of their routine care. All patients had Fibroscan performed on the day of surgery and at follow-up a mean of 13 months (± 6.3) later. The majority of patients were female (82%) with mean age of 42. Fibroscan was successful in 167 (88%) at baseline and 100% at follow up. Patients with a failed Fibroscan had higher body mass index (BMI) and alanine transaminase (ALT), but no difference in FIB-4/NAFLD score. Mean baseline Liver stiffness measurement was 5.1 kPa, with 87% of patients classified as no fibrosis and 4% as advanced fibrosis. Mean baseline controlled attenuation parameter was 291, with 78% having significant steatosis, 56% of which was moderate-severe. Significant fibrosis was associated with higher BMI and HbA1c. Significant steatosis was associated with higher BMI, ALT, triglycerides and insulin resistance. Mean follow up time was 12 months with weight loss of 25.7% and BMI reduction of 10.4 kg/m2. Seventy patients had repeat fibroscan with reductions in steatosis seen in 90% and fibrosis in 67%. Sixty-four percent had complete resolution of steatosis. Fibroscan can be performed reliably in bariatric cohorts and is useful at baseline and follow-up. Significant steatosis, but not fibrosis was seen in this cohort with substantial improvements post-surgery.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Christian Herder ◽  
Markku Peltonen ◽  
Per-Arne Svensson ◽  
Maren Carstensen ◽  
Peter Jacobson ◽  
...  

Introduction: Adiponectin has anti-inflammatory, insulin-sensitising and atheroprotective effects in rodents. Although serum adiponectin is uniformly downregulated in obesity, its clinical relevance in humans seems more complex. It is not known whether changes in circulating adiponectin predict type 2 diabetes, cardiovascular disease, cancer and mortality in an obese population. Hypothesis: We hypothesised that adiponectin levels are upregulated substantially after weight loss following bariatric surgery and that pronounced increases of adiponectin should offer better protection for individuals against type 2 diabetes. In addition, findings for type 2 diabetes should be compared to associations with cardiovascular disease, myocardial infarction, stroke, cancer and mortality. Methods: Serum concentrations of total adiponectin were measured in 3,223 participants of the Swedish Obese Subjects (SOS) Study (1,533 in the bariatric surgery group: 229 with gastric bypass, 1056 with vertical banded gastroplasty, 248 with adjustable gastric banding; 1,690 in the control group without surgery) at study baseline and after 2 years. Hazard ratios (HR) and 95% confidence intervals (CI) per 1 standard deviation (SD) of 2-year changes (concentration at year 2 - concentration at baseline) in adiponectin were calculated for incident type 2 diabetes, cardiovascular disease, myocardial infarction, stroke, cancer and mortality in the combined surgery group. Numbers of cases were 93, 122, 78, 55, 82 and 179, respectively. Median follow-up times ranged from 10 years for diabetes up to 16 years for mortality. Results: Mean (SD) levels of adiponectin at baseline were 7,453 (4,150) ng/ml in the combined surgery group and 8,247 (4,846) ng/ml in the control group. During the first 2 years of follow-up, adiponectin levels increased in the surgery group by 4,850 (5,387) ng/ml (parallel to a loss of 24% of body weight) and decreased slightly by 270 (2,650) ng/ml in the control group (parallel to a slight gain of 0.1% body weight). The degree of correlation between changes in adiponectin and weight loss in kg was more pronounced in the surgery groups compared with the control group (p=0.001 for interaction). Two-year increases in adiponectin in the surgery group were associated with decreased risk of type 2 diabetes (HR [95% CI] 0.61 [0.38-0.98], adjusted for baseline data for age, sex, BMI, lipids, blood pressure, alcohol consumption, smoking, anti-hypertensive drugs, glucose, insulin), but not with cardiovascular disease, myocardial infarction, stroke, cancer and mortality (adjusted HR between 0.89 and 1.05). Conclusions: Weight loss after bariatric surgery is paralleled by a substantial increase in circulating adiponectin. The degree of upregulation of adiponectin is associated with protection against future type 2 diabetes, but not with the incidence of cardiovascular outcomes, cancer or mortality.


2017 ◽  
Vol 3 (6) ◽  
Author(s):  
Lakshminarayanan Varadhan ◽  
Sushuma Kalidindi ◽  
Gurmit Gill ◽  
Hafsa Imran ◽  
Tracy Humphreys ◽  
...  

2021 ◽  
Author(s):  
Yashar Zeighami ◽  
Sylvain Iceta ◽  
Mahsa Dadar ◽  
Mélissa Pelletier ◽  
Mélanie Nadeau ◽  
...  

1.AbstractBackgroundMetabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique opportunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion. Previous studies found widespread changes in grey matter (GM) and white matter (WM) after bariatric surgery. However, findings regarding changes in spontaneous neural activity following surgery, as assessed with the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity of neural activity (ReHo), are scarce and heterogenous. In this study, we used a longitudinal design to examine the changes in spontaneous neural activity after bariatric surgery (comparing pre- to post-surgery), and to determine whether these changes are related to cardiometabolic variables.MethodsThe study included 57 participants with severe obesity (mean BMI=43.1±4.3kg/m2) who underwent sleeve gastrectomy (SG), biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB), scanned prior to bariatric surgery and at follow-up visits of 4 months (N=36), 12 months (N=29), and 24 months (N=14) after surgery. We examined fALFF and ReHo measures across 1022 cortical and subcortical regions (based on combined Schaeffer-Xiao parcellations) using a linear mixed effect model. Voxel-based morphometry (VBM) based on T1-weighted images was also used to measure GM density in the same regions. We also used an independent sample from the Human Connectome Project (HCP) to assess regional differences between individuals who had normal-weight (N=46) or severe obesity (N=46).ResultsWe found a global increase in the fALFF signal with greater increase within dorsolateral prefrontal cortex, precuneus, inferior temporal gyrus, and visual cortex. This effect was more significant 4 months after surgery. The increase within dorsolateral prefrontal cortex, temporal gyrus, and visual cortex was more limited after 12 months and only present in the visual cortex after 24 months. These increases in neural activity measured by fALFF were also significantly associated with the increase in GM density following surgery. Furthermore, the increase in neural activity was significantly related to post-surgery weight loss and improvement in cardiometabolic variables, such as insulin resistance index and blood pressure. In the independent HCP sample, normal-weight participants had higher global and regional fALFF signals, mainly in dorsolateral/medial frontal cortex, precuneus and middle/inferior temporal gyrus compared to the obese participants. These BMI-related differences in fALFF were associated with the increase in fALFF 4 months post-surgery especially in regions involved in control, default mode and dorsal attention networks.ConclusionsBariatric surgery-induced weight loss and improvement in metabolic factors are associated with widespread global and regional increases in neural activity, as measured by fALFF signal. These findings alongside the higher fALFF signal in normal-weight participants compared to participants with severe obesity in an independent dataset suggest an early recovery in the neural activity signal level after the surgery.


2018 ◽  
Vol 73 (2) ◽  
pp. 106-112 ◽  
Author(s):  
Daniel Antonio de Luis ◽  
Susana García Calvo ◽  
Juan Jose Lopez Gomez ◽  
Olatz Izaola ◽  
David Primo ◽  
...  

Introduction: Omentin-1 might play a role in the pathogenesis of insulin resistance and obesity. The aim of the present study was to evaluate the influence of weight loss after biliopancreatic diversion on serum omentin-1 concentrations. Material and Methods A Caucasian population of 24 morbid obese patients was analyzed before and after 12 months of a biliopancreatic diversion surgery. Biochemical and anthropometric evaluation were realized at basal visit and at 12 months. Body weight, fat mass, waist circumferences, blood pressure, fasting blood glucose, fasting insulin, insulin resistance (HOMA-IR), lipid concentrations and omentin-1 were measured. Results: After bariatric surgery and in both gender groups (males vs. females); BMI, weight, fat mass, waist circumference, blood pressure, glucose , total cholesterol, LDL cholesterol, triglycerides, HOMA-IR and fasting insulin decreased in a statistical manner from basal values. Omentin-1 levels increased after bariatric surgery and in both gender the improvement was similar (males vs. females); (delta: –87.1 ± 19.0 ng/dL; p = 0.02 vs. –93.8 ± 28.1 ng/dL; p = 0.03). In the multiple regression analysis adjusted by age and sex; BMI kg/m2 (Beta –0.32: 95% CI –3.98 to –0.12) and insulin UI/L (Beta –0.41: 95% CI –8.38 to –0.16) remained in the model with basal omentin-1 levels as dependent variable. The regression model with post-surgery omentin-1 levels as dependent variable showed as independent variables BMI kg/m2 (Beta –0.13: 95% CI –7.69 to –0.09) and insulin UI/L (Beta –0.24: 95% CI –5.69 to –0.08), too. Conclusion: This study showed a significant increase in omentin-1 levels after weight loss secondary biliopancreatic diversion surgery. A weak negative correlation with BMI and basal insulin levels was detected.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Zhanxuan Wu ◽  
Karl Fraser ◽  
Marlena Kruger ◽  
Garth Cooper ◽  
Anne-Thea McGill ◽  
...  

Abstract Objectives Plasma levels of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) phenylalanine (phe) and tyrosine (tyr) have been associated with obesity, insulin resistance and risk of type 2 diabetes. This study aimed to investigate the response of circulating plasma and tissue levels of BCAA and AAA to weight loss, and to correlate the level of these metabolites in plasma and tissue in obese women. Methods 28 obese (mean BMI 46.2 kg/m2) women underwent low energy diet (LED)-induced weight loss (−9.2 ± 4.2 kg) followed by bariatric surgery-induced weight loss (−23.6 ± 2.5 kg). Plasma at baseline (t0), post-LED/pre-surgery (t1) and 6-month post-surgery (t2) as well as biopsies of subcutaneous abdomen adipose tissue (SAfat), superficial thigh adipose tissue (Tfat) and vastus lateralis thigh muscle (Tmuscle) at both t1 and t2 were collected, and profiled using mass spectrometry-based metabolomics approach. Paired t-tests were applied to assess between-timepoint differences, and Pearson correlation used to calculate correlation coefficient of metabolite levels between plasma and tissue. Results Plasma BCAA and AAA were all significantly reduced post-LED at t1 (fold-change of 0.76–0.85 for val, leu, ile, tyr and phe, P < 0.05) and 6-month post-surgery at t2 (fold-change of 0.74–0.85 for val, leu, ile, tyr and phe, P < 0.05) as compared to baseline t0; but not significant between t1 and t2, although trends of decrease were observed. Among the 3 tissue biopsies, only SAfat showed significantly decreased levels of tyr, leu and ile at t2 compared to t1 (fold-change for tyr 0.63, leu 0.66, ile 0.68, P < 0.05). In addition, plasma levels of val and ile were correlated with Tfat levels at both t1 and t2 (r2 = 0.47–0.57), and that of val, ile and leu were correlated with Tmuscle at t1 only (r2 = 0.64–0.67). Conclusions Circulating levels of BCAA and AAA were decreased by weight loss interventions. The decrease following an LED program was sustained after bariatric surgery without further significant decrease. Bariatric surgery also decreased BCAA levels in SAfat; moreover, our data suggested that plasma BCAA levels correlated well with peripheral tissue Tfat and Tmuscle. Funding Sources The New Zealand National Science Challenge High-Value Nutrition program.


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