scholarly journals Major microbiota dysbiosis in severe obesity: fate after bariatric surgery

Gut ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Judith Aron-Wisnewsky ◽  
Edi Prifti ◽  
Eugeni Belda ◽  
Farid Ichou ◽  
Brandon D Kayser ◽  
...  

ObjectivesDecreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.DesignSixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.ResultsLow gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.ConclusionsWe identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity.Trial registration numberNCT01454232.

Gut ◽  
2022 ◽  
pp. gutjnl-2021-325753
Author(s):  
Eugeni Belda ◽  
Lise Voland ◽  
Valentina Tremaroli ◽  
Gwen Falony ◽  
Solia Adriouch ◽  
...  

ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.


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.


2021 ◽  
Vol 10 (17) ◽  
pp. 3879
Author(s):  
María Insenser ◽  
Nuria Vilarrasa ◽  
Joan Vendrell ◽  
Héctor F. Escobar-Morreale

Bariatric surgery restores glucose tolerance in many, but not all, severely obese subjects with type 2 diabetes (T2D). We aimed to evaluate the plasma protein profiles associated with the T2D remission after obesity surgery. We recruited seventeen women with severe obesity submitted to bariatric procedures, including six non-diabetic patients and eleven patients with T2D. After surgery, diabetes remitted in 7 of the 11 patients with T2D. Plasma protein profiles at baseline and 6 months after bariatric surgery were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight coupled to mass spectrometry (MALDI-TOF/TOF MS). Remission of T2D following bariatric procedures was associated with changes in alpha-1-antichymotrypsin (SERPINA 3, p < 0.05), alpha-2-macroglobulin (A2M, p < 0.005), ceruloplasmin (CP, p < 0.05), fibrinogen beta chain (FBG, p < 0.05), fibrinogen gamma chain (FGG, p < 0.05), gelsolin (GSN, p < 0.05), prothrombin (F2, p < 0.05), and serum amyloid p-component (APCS, p < 0.05). The resolution of diabetes after bariatric surgery is associated with specific changes in the plasma proteomic profiles of proteins involved in acute-phase response, fibrinolysis, platelet degranulation, and blood coagulation, providing a pathophysiological basis for the study of their potential use as biomarkers of the surgical remission of T2D in a larger series of severely obese patients.


2017 ◽  
Vol 125 (05) ◽  
pp. 301-306 ◽  
Author(s):  
Britta Wilms ◽  
Barbara Ernst ◽  
Martin Thurnheer ◽  
Christina Spengler ◽  
Bernd Schultes

Abstract Both severe obesity and type 2 diabetes (T2DM) are associated with reduced pulmonary function and reduced cardiorespiratory fitness. We investigated whether T2DM further aggravates the impaired pulmonary function and cardiorespiratory fitness in subjects with severe obesity. In this cross-sectional study pulmonary function (forced expiratory volume within 1 s, FEV1; vital capacity, VC) was assessed in 65 severely obese subjects with T2DM (T2DM group) and 65 severely obese subjects without T2DM (non-T2DM group), pairwise matched for sex, age, weight, and height. In 30 of the matched pairs, cardiorespiratory fitness was assessed by an incremental bicycle test (peak workload, Wpeak, oxygen uptake, V̇O2,peak). FEV1 and VC did not differ between the T2DM and non-T2DM group (all p≥0.110), whereas Wpeak and V̇O2,peak - absolute values as well as relative to body mass - were significantly lower in subjects with T2DM compared to those without T2DM (all p≤0.030). Objective markers of maximal exertion, i. e., maximal heart rate and respiratory exchange ratio, did not differ between the 2 groups (both p≥0.245). The presence of T2DM in subjects with severe obesity is associated with lower cardiorespiratory fitness but with no further reduction in pulmonary function compared to subjects with severe obesity but without T2DM. While the cause-effect relationship of this association is not yet clear, these findings highlight the interplay between cardiorespiratory fitness and metabolic health, even in subjects with severe obesity.


2008 ◽  
Vol 93 (11_supplement_1) ◽  
pp. s89-s96 ◽  
Author(s):  
Walter J. Pories

ABSTRACT Context Over 23 million Americans are afflicted with severe obesity, i.e. their body mass index (in kilograms per square meter) values exceed 35. Of even greater concern is the association of the adiposity with comorbidities such as diabetes, hypertension, cardiopulmonary failure, asthma, pseudotumor cerebri, infertility, and crippling arthritis. Objective: Diets, exercise, behavioral modification, and drugs are not effective in these individuals. This article examines the effect of surgery on the control of the weight and the comorbidities, as well as the safety of these operations. Interventions: Although the article focuses on the outcomes of the three most commonly performed operations, i.e. adjustable gastric banding, the gastric bypass, and the biliopancreatic bypass with duodenal switch, it aims for perspective with the inclusion of abandoned and current investigational procedures, a review of the complications, and an emphasis on the appropriate selection of patients. Positions: Ample evidence, including controlled randomized studies, now document that bariatric surgery produces durable weight loss exceeding 100 lb (46 kg), full and long-term remission of type 2 diabetes in over 80% with salutary effects on the other comorbidities as well with significant reductions in all-cause mortality. Although the severely obese present with serious surgical risks, bariatric surgery is performed safely with a 0.35% 90-d mortality in Centers of Excellence throughout the United States—similar to the complication rates after cholecystectomy. Conclusions Until better approaches become available, bariatric surgery is the therapy of choice for patients with severe obesity.


2016 ◽  
Vol 22 ◽  
pp. 159
Author(s):  
Carolina Casellini ◽  
Joshua Edwards ◽  
Henri Parson ◽  
Kim Hodges ◽  
David Lieb ◽  
...  

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.


2021 ◽  
Author(s):  
Kajsa Sjöholm ◽  
Lena MS Carlsson ◽  
Per-Arne Svensson ◽  
Johanna C. Andersson-Assarsson ◽  
Felipe Kristensson ◽  
...  

<b>OBJECTIVE</b> <p>Obesity and type 2 diabetes are associated with serious, adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study. </p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of which underwent bariatric surgery, and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years). </p> <p><b>RESULTS</b></p> <p>During follow-up, the incidence rate for first-time cancer was 9.1 per 1000-person-years (95% CI, 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1000-person-years (95% CI, 11.2-17.7) in patients treated with usual obesity care (HRadj=0.63; 95% CI 0.44-0.89, p=0.008). Moreover, surgery was associated with reduced cancer incidence in women (HRadj=0.58; 0.38-0.90, p=0.016), although the sex-treatment interaction was non-significant (p=0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (HRadj=0.40; 95% CI 0.22-0.74, p=0.003).</p> <p><b>CONCLUSIONS</b></p> <p>These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes, and that durable diabetes remission is associated with reduced cancer risk. </p>


Cardiology ◽  
2007 ◽  
Vol 109 (4) ◽  
pp. 241-248 ◽  
Author(s):  
Vitantonio Di Bello ◽  
Ferruccio Santini ◽  
Andrea Di Cori ◽  
Andrea Pucci ◽  
Enrica Talini ◽  
...  

2016 ◽  
Vol 101 (12) ◽  
pp. 1161-1167 ◽  
Author(s):  
Neil Wright ◽  
Jerry Wales

Approximately 3% of children and adolescents in the UK have severe obesity. The incidence of cardiovascular risk factors such as hypertension, hyperinsulinism and hyperlipidaemia approaches 20% in such individuals. Lifestyle intervention programmes and pharmacotherapy are effective in some individuals, but the relapse rate is high. In exceptional cases, bariatric surgery is effective. This review outlines the scale of the problem, highlights those at risk and discusses referral, current services, appropriate screening and therapeutic interventions.


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