Role of gut microbiota,bile acids and their cross‐talk in the effects of bariatric surgery on obesity and type 2 diabetes

Type 2 diabetes mellitus is becoming increasingly prevalent worldwide, and has become one of the greatest threats to global health. Bariatric surgery was initially designed to achieve weight loss, and subsequently was noted to induce improvements or remission of type 2 diabetes. Currently, these bariatric operations, such as Roux‐en‐Y gastric bypass and sleeve gastrectomy, are the most effective procedures for the treatment of obesity and type 2 diabetes mellitus worldwide. However, the specific mechanism mediating the beneficial effects of metabolic surgery has remained largely unknown. Those mechanical explanations, such as restriction and malabsorption, are challenged by accumulating evidence from human and animal models of these procedures, which points to the weight‐independent factors, such as hormones, bile acids, gut microbiota, nervous system and other potential underlying mechanisms. A growing body of evidence suggests that gut microbiota are associated with the development of several metabolic disorders, and bile acids and FXR signaling are important for the metabolic benefits of bariatric surgery. Given the close relationship between bacteria and bile acids, it is reasonable to propose that microbiota–bile acid interactions play a role in the mechanisms underlying the effects of metabolic surgery.     

青少年肥胖症代谢手术后3年效应观察与分析

目的探究青少年肥胖症病人接受减重代谢手术后中期效益及影响。 方法回顾性分析2014年11月至2015年10月于长春嘉和外科医院接受减重代谢手术的16例青少年肥胖症患者（13~21岁）的临床资料,对他们术前及术后3年间的体重、体质量指数（BMI）、甘油三酯（TC）、高密度脂蛋白（HDL）及低密度脂蛋白（LDL）进行统计分析。 结果16名入组患者的平均体重、BMI、空腹TC、LDL在术后3年均有不同幅度下降,平均空腹HDL有所升高,数据分析均有统计学意义（P<0.05）。 结论减重代谢手术可以明确并且持续性地减轻青少年肥胖症病人的体重,同时改善血脂异常问题。青少年一旦达到肥胖II级应当尽早手术。     

Gastrointestinal changes after bariatric surgery

Severe obesity is a preeminent health care problem that impacts overall health and survival. The most effective treatment for severe obesity is bariatric surgery, an intervention that not only maintains long-term weight loss but also is associated with improvement or remission of several comorbidies including type 2 diabetes mellitus. Some weight loss surgeries modify the gastrointestinal anatomy and physiology, including the secretions and actions of gut peptides. This review describes how bariatric surgery alters the patterns of gastrointestinal motility, nutrient digestion and absorption, gut peptide release, bile acids and the gut microflora, and how these changes alter energy homeostasis and glucose metabolism.     

Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome

Clinical studies have indicated that circulating bile acid(BA) concentrations increase following bariatric surgery, especially following malabsorptive procedures such as Roux-en-Y gastric bypasses(RYGB). Moreover, total circulating BA concentrations in patients following RYGB are positively correlated with serum glucagonlike peptide-1 concentrations and inversely correlated with postprandial glucose concentrations. Overall, these data suggest that the increased circulating BA concentrations following bariatric surgery- independently of calorie restriction and body-weight loss- could contribute, at least in part, to improvements in insulin sensitivity, incretin hormone secretion, and postprandial glycemia, leading to the remission of type-2 diabetes(T2DM). In humans, the primary and secondary BA pool size is dependent on the rate of biosynthesis and the enterohepatic circulation of BAs, as well as on the gut microbiota, which play a crucial role in BA biotransformation. Moreover, BAs and gut microbiota are closely integrated and affect each other. Thus, the alterations in bile flow that result from anatomical changes caused by bariatric surgery and changes in gutmicrobiome may influence circulating BA concentrations and could subsequently contribute to T2 DM remission following RYGB. Research data coming largely from animal and cell culture models suggest that BAs can contribute, via nuclear farnezoid X receptor(FXR) and membrane G-protein-receptor(TGR-5), to beneficial effects on glucose metabolism. It is therefore likely that FXR, TGR-5, and BAs play a similar role in glucose metabolism following bariatric surgery in humans. The objective of this review is to discuss in detail the results of published studies that show how bariatric surgery affects glucose metabolism and subsequently T2 DM remission.     

Modelling the long-term outcomes of bariatric surgery: A review of cost-effectiveness studies

Obesity, defined as BMI ≥30 kg/m², affects over 30% of the United States adult population and has been declared an epidemic by the Centers for Disease Control. Bariatric surgery is a treatment option to reduce excess weight and is available to individuals with BMI greater than 40 kg/m², or 35 kg/m² with obesity-related comorbidities. As surgical options have become more common, researchers have analysed the long-term cost-effectiveness of these procedures. However, the follow-up data on patients is limited, and modelers need to forecast lifetime costs and outcomes for this chronic disease. In this chapter, we conduct a systematic literature review of cost-effectiveness studies on bariatric surgery to understand the forecasting methods used in practice. We identified six unique studies, which used statistical models, Markov models, or assumptions to forecast lifetime outcomes. We discuss each of the approaches, so clinicians, policy-makers, and payers can make informed interpretations based on the models.     

Efficacy and effects of bariatric surgery in the treatment of obesity: Network meta-analysis of randomized controlled trials

AimsBariatric surgery (BS) is recommended for subjects with a Body Mass Index (BMI) over of 40 kg/m² or with a BMI between 35 and 40 kg/m² with obesity-related comorbidities. Aim of the study was to compare different types of BS with medical therapy (MT) for the treatment of obesity.Data synthesisWe conducted a network-meta-analysis (NMA) including randomized clinical trials comparing different BS techniques versus MT in people with obesity, with a duration ≥24 weeks (PROSPERO, #CRD42020160359). Primary endpoint was BMI. Indirect comparisons of different types of surgery were performed by NMA. Types of BS included: laparoscopic adjustable gastric banding (LAGB), Roux-en-Y gastric bypass, sleeve gastrectomy (SG), bilio-pancreatic diversion (BPD); greater curvature plication (GCP); one-anastomosis gastric bypass (OAGB); Laparoscopic Vertical Banded Gastroplasty (LVBG) and duodenal switch (DS). 43 trials were retrieved in this metanalysis. BS was associated with a significant reduction in BMI, systolic blood pressure, triglyceride and fasting glucose, and with a significant increase of HDL cholesterol when compared to MT. In direct comparisons, RYGB was more effective than LAGB, LVBG, and GCP, but less effective than DS, whereas LAGB was less effective than LVBG and SG. In the NMA, DS and BPD appeared to be more effective than other procedures.ConclusionsBS produces a greater weight loss than MT in morbidly obese patients, inducing a greater improvement of obesity-associated metabolic parameters. Available data are insufficient to assess the effect of BS on mortality. Different surgical procedures are heterogeneous for efficacy and safety.     

Anti-sRAGE autoimmunity in obesity: Downturn after bariatric surgery is independent of previous diabetic status

AimMorbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients.MethodsAfter exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1 year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors.ResultsCompared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P < 0.001). At 1 year after gastric bypass, sRAGE and anti-sRAGE were decreased (P < 0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P = 0.02).ConclusionIndependently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.     

Helicobacter pylori infection in obesity and its clinical outcome after bariatric surgery

The present review summarizes the prevalence and active clinical problems in obese patients with Helicobacter pylori(H.pylori)infection,as well as the outcomes after bariatric surgery in this patient population.The involvement of H.pylori in the pathophysiology of obesity is still debated.It may be that the infection is protective against obesity,because of the gastritis-induced decrease in production and secretion of the orexigenic hormone ghrelin.However,recent epidemiological studies have failed to show an association between H.pylori infection and reduced body mass index.H.pylori infection might represent a limiting factor in the access to bariatric bypass surgery,even if highquality evidence indicating the advantages of preoperative H.pylori screening and eradication is lacking.The clinical management of infection is complicated by the lower eradication rates with standard therapeutic regimens reported in obese patients than in the normalweight population.Prospective clinical studies to ameliorate both H.pylori eradication rates and control the clinical outcomes of H.pylori infection after different bariatric procedures are warranted.     

减重代谢手术并发症单中心总结

目的 总结山东大学附属济南市中心医院胃肠外科减重代谢手术的并发症及处理方法.方法 回顾性分析自2013年11月至2018年11月在山东大学附属济南市中心医院胃肠外科接受减重代谢手术的230例患者的病例资料,其中行腹腔镜Roux-en-Y胃旁路术(LRYGB)57例和腹腔镜袖状胃切除术(LSG)173例,总结分析并发症、...     

Gut microbiota and metabolic syndrome

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome,as confirmed by studies conducted both on humans and animal models.Gut microbial composition and functions are strongly influenced by diet.This complex intestinal“superorganism”seems to affect host metabolic balance modulating energy absorption,gut motility,appetite,glucose and lipid metabolism,as well as hepatic fatty storage.An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of“metabolic endotoxemia”,leading to systemic inflammation and insulin resistance.Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition,that seem to affect the success,or the inefficacy,of treatment strategies.Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity,thus,ameliorating metabolic balance and promoting weight loss.However,further evidence is needed to better understand their clinical impact and therapeutic use.     

Changes in abdominal fat depots after bariatric surgery are associated with improved metabolic profile

Background and aimsObesity associated with a change in the quantity and quality of fat depots. Using computed tomography (CT), we analyzed abdominal fat depots in patients with obesity after bariatric surgery according to their metabolic health status.Methods and resultsWe recruited 79 individuals with metabolically unhealthy obesity before bariatric surgery and compared them with age-sex matched healthy controls. The volume and fat attenuation index (FAI) of fat depots were measured using CT scans that were conducted prior to and a year after bariatric surgery. ‘Metabolically healthy’ was defined as having no hypertension, normal fasting glucose and a waist-to-hip ratio of <1.05 for men and <0.95 for women. Individuals who achieved a metabolic health status conversion (MHC) (n = 29, 37%)—from unhealthy to healthy—were younger (p < 0.001) as compared to individuals without MHC. Pre-surgery BMI and reduction of BMI did not differ between the two groups (p = 0.099, p = 0.5730). Bariatric surgery reduced the volume and increased the FAI of fat depots. Baseline lower abdominal periaortic adipose tissue (AT) volume (p = 0.014) and great percent reduction in renal sinus AT volume after surgery (p = 0.019) were associated with MHC after surgery. Increased intraperitoneal AT FAI (p = 0.031) was also associated with MHC.ConclusionMHC was not associated with improvement in general obesity, based on indicators such as reduction of BMI after surgery. Weight reduction induced specific abdominal fat depot changes measured by CT are positively associated with MHC.     

East Asian perspectives in metabolic and bariatric surgery

The prevalence of diabetes and obesity continues to rise in East Asia. As the risk of diabetes increases at a lower body mass index (BMI) in East Asians than in Europeans, the threshold of BMI values for metabolic and bariatric surgery (MBS) is lower in East Asians. MBS is considered upon reaching a BMI of 27.5 kg/m² and is recommended at a BMI of ≥ 32.5 kg/m², depending on the status of glucose homeostasis. The most commonly performed MBS in East Asia is sleeve gastrectomy, followed by Roux‐en‐Y gastric bypass (RYGB). Because the incidence of gastric cancer is higher in East Asia than in other regions, concerns regarding surveillance for gastric cancer might be related to a preference for sleeve gastrectomy over RYGB in this region. Even though there is a paucity of data on direct comparisons of the efficacy of MBS among different ethnic groups, the degree of weight reduction in East Asians is not inferior to other ethnic groups. Moreover, studies suggest that the diabetes remission rate in East Asians seemed to be higher than in other ethnic groups. Future studies involving multiethnic groups are necessary to identify possible ethnic differences in diabetes remission and to determine the appropriate BMI threshold for MBS according to ethnicity.     

减重手术对肥胖合并亚临床甲状腺功能减退症影响的Meta分析

目的系统评价减重手术对肥胖相关的亚临床甲状腺功能减退症（SH）的影响。 方法检索PubMed、Embase、Cochrane Library、万方、中国知网等数据库关于减重手术对肥胖合并SH影响的相关研究,检索起止时间均从建库至2019年4月。采用MINORS （methodological index for non-randomized studies）条目进行纳入文献质量评价,使用RevMan 5.3软件进行Meta分析。 结果共纳入5项队列研究。Meta分析结果示：减重手术可促使合并SH的肥胖患者血清TSH下降（SMD =1.94,95%CI：1.59～2.30,P<0.00001）,而对FT4无影响（SMD=0.15,95%CI：-0.77～1.08,P=0.74）。减重手术可改善肥胖合并SH（OR=49.75, 95%CI: 15.08～164.15, P<0.00001）。 结论减重手术可以明显改善肥胖合并SH。     

Symptoms,endoscopic findings and reflux monitoring results in candidates for bariatric surgery

BackgroundGastroesophageal reflux disease (GERD) is common in patients with obesity. Diagnosing GERD is important as bariatric operations have different influence on GERD. We assessed reflux symptoms and objective findings prior to surgery.MethodsWork-up included esophageal symptoms quantification by VAS-scores, esophagogastroduodenoscopy (EGD) and 24-h impedance-pH (imp-pH) monitoring off PPI therapy. Imp-pH was classified as abnormal if either %time pH < 4 was abnormal, total number of reflux episodes was elevated or symptom index (SI) was positive.ResultsAmong 100 consecutive patients (68F, age 40 ± 11 years, BMI 44.9 ± 6.9 kg/m²) 54% reported heartburn and/or regurgitation, 71% had objective evidence of GERD (38% endoscopic lesions and 33% only abnormal imp-pH results). Imp-pH was superior to EGD in identifying GERD (sensitivity 85% vs. 54%, p < 0.01). Symptomatic and asymptomatic patients had similar prevalence of esophageal lesions (37% vs. 39%) and abnormal imp-pH findings (68% vs. 50%). Sixty nine percent of patients with abnormal %time pH < 4 had a normal number of reflux episodes.ConclusionHalf of patients with obesity reported typical GERD symptoms and >70% had evidence of GERD. Poor acid clearance was the main mechanisms. Since typical reflux symptoms don’t predict objective findings, endoscopy and reflux monitoring should be part of the surgery work-up especially before restrictive procedures.     

Gut microbiota after Roux‐en‐Y gastric bypass and sleeve gastrectomy in a diabetic rat model: Increased diversity and associations of discriminant genera with metabolic changes

Recent work with gut microbiota after bariatric surgery is limited, and the results have not been in agreement. Given the role of the gut microbiota in regulating host metabolism, we explored the effect of Roux‐en‐Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the modifications of gut microbiota with regard to the potential influence of food intake and/or weight loss and examined their links with host metabolism. Zucker diabetic fatty rats were divided into the following groups: RYGB; sham‐operated with pair‐fed as RYGB; sham‐operated fed ad libitum ; and SG. The metabolic effects and gut microbiota profile were analyzed 10 weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10 weeks compared with sham‐operated groups. RYGB induced a marked higher relative abundance of Proteobacteria/Gammaproteobacteria and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, whereas SG resulted in more abundant Actinobacteria compared with other groups. Most of the 12 discriminant genera correlated with changes in metabolic phenotype, but only 28.6% of these correlations were independent of weight, and 4 discriminant genera still negatively correlated with serum insulin level independent of food intake and weight loss after RYGB. These data demonstrate that RYGB and SG surgery produced similar diversity but different microbiota compositions changes in Zucker diabetic fatty rats. These findings stimulate deeper explorations of functions of the discriminate microbiota and the mechanisms linking postsurgical modulation of gut microbiota and improvements in insulin resistance.     

Nutrition,the gut microbiome and the metabolic syndrome

Metabolic syndrome is a lifestyle disease, determined by the interplay of genetic and environmental factors. Obesity is a significant risk factor for development of the metabolic syndrome, and the prevalence of obesity is increasing due to changes in lifestyle and diet. Recently, the gut microbiota has emerged as an important contributor to the development of obesity and metabolic disorders, through its interactions with environmental (e.g. diet) and genetic factors. Human and animal studies have shown that alterations in intestinal microbiota composition and shifts in the gut microbiome towards increased energy harvest are associated with an obese phenotype. However, the underlying mechanisms by which gut microbiota affects host metabolism still need to be defined.In this review we discuss the complexity surrounding the interactions between diet and the gut microbiota, and their connection to obesity. Furthermore, we review the literature on the effects of probiotics and prebiotics on the gut microbiota and host metabolism, focussing primarily on their anti-obesity potential.     

Audit of nutritional and dietary outcomes of bariatric surgery patients

Bariatric surgery is the most effective means of achieving sustainable weight loss for the morbidly obese but resultant gastrointestinal functional changes and altered diet may lead to a number of eating and nutritional problems. This audit was conducted to evaluate Guernsey outcomes in relation to UK national standards and to determine the adequacy of current dietetic provision. A postal questionnaire was sent to 177 patients. Sixty‐eight responded (48 gastric bypass, 15 banding and five other procedures). Mean body mass index preoperatively was 44.2 (five had body mass index <35). Five respondents (7%) had received preoperative and 26 post‐operative dietary advice. Only 12 (18%) received any dietetic follow‐up. Only one patient had any psychological support. Mean maximal weight loss and regain was 42.7 kg and 4.5 kg, respectively. Micronutrient supplementation and monitoring was variable. Deficiencies of B₁₂ (44%), iron (25%), vitamin D (10.2%) and folate (6.2%) were recorded. Problems with food intolerances were common and often protracted. The majority of respondents expressed satisfaction with the procedure, but many recognized that it had not solved their food‐related issues. There was dissatisfaction with dietetic intervention. Overall, current treatment was shown to fall short of UK standards. A number of recommendations have been made to improve future outcomes, including re‐audit and improved dietetic service provision.     

肠道菌群与肥胖和糖尿病的关系

人的胃肠道内寄居着种类繁多的单细胞微生物,称为肠道菌群.基因、出生方式、婴幼儿喂养模式、抗生素应用、卫生居住条件以及长期的饮食习惯有助于塑造肠道菌群的组成.越来越多的动物和人体研究表明肠道菌群与肥胖和2型糖尿病密切相关.肠道菌群可通过宿主能量代谢、免疫系统及炎性反应等影响代谢综合征及2型糖尿病的发生、发展.干预肠道菌群有可能成为防治肥胖及糖尿病的新靶点.