Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients.
ABSTRACT: Bariatric surgery is highly successful in improving health compared to conventional dietary treatments. It has been suggested that the gut microbiota is a relevant factor in weight loss after bariatric surgery. Considering that bariatric procedures cause different rearrangements of the digestive tract, they probably have different effects on the gut microbiota. In this study, we compared the impact of medical treatment, sleeve gastrectomy and Roux-en-Y gastric bypass on the gut microbiota from obese subjects. Anthropometric and clinical parameters were registered before, 6 and 12 months after treatment. Fecal samples were collected and microbiota composition was studied before and six months post treatment using 16S rRNA gene sequencing and qPCR. In comparison to dietary treatment, changes in intestinal microbiota were more pronounced in patients subjected to surgery, observing a bloom in Proteobacteria. Interestingly, Bacteroidetes abundance was largely different after six months of each surgical procedure. Furthermore, changes in weight and BMI, or glucose metabolism, correlated positively with changes in these two phyla in these surgical procedures. These results indicate that distinct surgical procedures alter the gut microbiota differently, and changes in gut microbiota might contribute to health improvement. This study contributes to our understanding of the impact of weight loss surgery on the gut microbiota, and could be used to replicate this effect using targeted therapies.
Project description:Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls. By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery.
Project description:<h4>Backgruound</h4>Current evidence support that the gut microbiota plays a potential role in obesity. Bariatric surgery can reduce excess weight and decrease the risk of life-threatening weight-related health problems and may also influence gut microbiota. In this study, we aimed to investigate the changes in gut microbiota before and after bariatric surgery and evaluate the association of the gut microbial shift and altered body mass index (BMI) after bariatric surgery.<h4>Methods</h4>Between January 2019 and July 2020, stools from 58 patients scheduled for bariatric surgery were collected. Six months after bariatric surgery, stools from 22 of these patients were re-collected, and the changes in gut microbiota before and after bariatric surgery were evaluated. In addition, the differences in gut microbiota between patients with severe obesity (BMI >35 kg/m2, n=42) and healthy volunteers with normal BMI (18.8 to 22.8 kg/m2, n=41) were investigated.<h4>Results</h4>The gut microbiota of patients who underwent bariatric surgery showed increased α-diversity and differed β-diversity compared with those before surgery. Interestingly, Blautia was decreased and Bacteriodes was increased at the genus level after bariatric surgery. Further, the Blautia/Bacteroides ratio showed a positive correlation with BMI. To validate these results, we compared the gut microbiota from severely obese patients with high BMI with those from healthy volunteers and demonstrated that the Blautia/Bacteroides ratio correlated positively with BMI.<h4>Conclusion</h4>In the gut microbial analysis of patients who underwent bariatric surgery, we presented that the Blautia/Bacteroides ratio had changed after bariatric surgery and showed a positive correlation with BMI.
Project description:Little is known about the influence of gastric microbiota on host metabolism, even though the stomach plays an important role in the production of hormones involved in body weight regulation and glucose homeostasis. Proton pump inhibitors (PPIs) and Helicobacter pylori alter gut microbiota, but their impact on gastric microbiota in patients with obesity and the influence of these factors on the metabolic response to bariatric surgery is not fully understood. Forty-one subjects with morbid obesity who underwent sleeve gastrectomy were included in this study. The H. pylori group was established by the detection of H. pylori using a sequencing-based method (<i>n</i> = 16). Individuals in whom H. pylori was not detected were classified according to PPI treatment. Gastric biopsy specimens were obtained during surgery and were analyzed by a high-throughput-sequencing method. Patients were evaluated at baseline and 3, 6, and 12 months after surgery. β-Diversity measures were able to cluster patients according to their gastric mucosa-associated microbiota composition. H. pylori and PPI treatment are presented as two important factors for gastric mucosa-associated microbiota. H. pylori reduced diversity, while PPIs altered β-diversity. Both factors induced changes in the gastric mucosa-associated microbiota composition and its predicted functions. PPI users showed lower percentages of change in the body mass index (BMI) in the short term after surgery, while the H. pylori group showed higher glucose levels and lower percentages of reduction in body weight/BMI 1 year after surgery. PPIs and H. pylori colonization could modify the gastric mucosa-associated microbiota, altering its diversity, composition, and predicted functionality. These factors may have a role in the metabolic evolution of patients undergoing bariatric surgery. <b>IMPORTANCE</b> The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied. In this study, we highlight the impact of these factors on the gastric microbiota composition. Moreover, proton pump inhibitor treatment and the presence of Helicobacter pylori could have an influence on bariatric surgery outcomes, mainly on body weight loss and glucose homeostasis. Deciphering the relationship between gastric hormones and gastric microbiota and their contributions to bariatric surgery outcomes paves the way to develop gut manipulation strategies to improve the metabolic success of bariatric surgery.
Project description:Bariatric surgery is emerging as a powerful weapon against severe obesity and type 2 diabetes mellitus (T2DM). Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to treat T2DM, especially in light of accumulating evidence that surgery with gastrointestinal manipulations may result in T2DM remission (metabolic surgery). The major mechanisms mediating the weight loss-independent effects of bariatric surgery comprise effects on tissue-specific insulin sensitivity, β-cell function and incretin responses, changes in bile acid composition and flow, modifications of gut microbiota, intestinal glucose metabolism and increased brown adipose tissue metabolic activity. Shorter T2DM duration, better preoperative glycemic control and profound weight loss, have been associated with higher rates of T2DM remission and lower risk of relapse. In the short and medium term, a significant amount of weight is lost, T2DM may completely regress, and cardiometabolic risk factors are dramatically improved. In the long term, metabolic surgery may achieve durable weight loss, prevent T2DM and cancer, improve overall glycemic control while leading to significant rates of T2DM remission, and reduce total and cause-specific mortality. The gradient of efficacy for weight loss and T2DM remission comparing the four established surgical procedures is biliopancreatic diversion >Roux-en-Y gastric bypass >sleeve gastrectomy >laparoscopic adjustable gastric banding. According to recently released guidelines, bariatric surgery should be recommended in diabetic patients with class III obesity, regardless of their level of glycemic control, and patients with class II obesity with inadequately controlled T2DM despite lifestyle and optimal medical therapy. Surgery should also be considered in patients with class I obesity and inadequately controlled hyperglycemia despite optimal medical treatment.
Project description:OBJECTIVE:Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development. DESIGN:A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed. RESULTS:Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight. CONCLUSION:Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further.
Project description:Bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective interventions available for sustained weight loss and improved glucose metabolism. Bariatric surgery alters the enterohepatic bile acid circulation, resulting in increased plasma bile levels as well as altered bile acid composition. While it remains unclear why both VSG and RYGB can alter bile acids, it is possible that these changes are important mediators of the effects of surgery. Moreover, a molecular target of bile acid synthesis, the bile acid-activated transcription factor FXR, is essential for the positive effects of VSG on weight loss and glycemic control. This Perspective examines the relationship and sequence of events between altered bile acid levels and composition, FXR signaling, and gut microbiota after bariatric surgery. We hypothesize that although bile acids and FXR signaling are potent mediators of metabolic function, unidentified downstream targets are the main mediators behind the benefits of weight-loss surgery. One of these targets, the gut-derived peptide FGF15/19, is a potential molecular and therapeutic marker to explain the positive metabolic effects of bariatric surgery. Focusing research efforts on identifying these complex molecular mechanisms will provide new opportunities for therapeutic strategies to treat obesity and metabolic dysfunction.
Project description:The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery.
Project description:Bariatric surgery is the only procedure to obtain and maintain weight loss in the long term, although the mechanisms driving these benefits are not completely understood. In the last years, gut microbiota has emerged as one of the drivers through its metabolites, especially secondary bile acids. In the current study, we have compared the gut microbiota and the bile acid pool, as well as anthropometric and biochemical parameters, of patient with morbid obesity who underwent bariatric surgery by two different techniques, namely Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Gut microbiota populations differed after the respective procedures, particularly with respect to the <i>Enterobacteriaceae</i> family. Both techniques resulted in changes in the bile acids pool, but RYGB was the procedure which suffered the greatest changes, with a reduction in most of their levels. <i>Blautia</i> and <i>Veillonella</i> were the two genera that more relationships showed with secondary bile acids, indicating a possible role in their formation and inhibition, respectively. Correlations with the anthropometric and biochemical variables showed that secondary bile acids could have a role in the amelioration of the glucose and HDL-cholesterol levels. Thus, we have observed a possible relationship between the interaction of the bile acids pool metabolized by the gut microbiota in the metabolic improvements obtained by bariatric surgery in the frame of morbid obesity, deserving further investigation in greater cohorts to decipher the role of each bile acid in the homeostasis of the host for their possible use in the development of microbiota-based therapeutics, such as new drugs, postbiotics or probiotics.
Project description:Gut microbiota has been shown to have an important influence on host health. The microbial composition of the human gut microbiota is modulated by diet and other lifestyle habits and it has been reported that microbial diversity is altered in obese people. Obesity is a worldwide health problem that negatively impacts the quality of life. Currently, the widespread treatment for obesity is bariatric surgery. Interestingly, gut microbiota has been shown to be a relevant factor in effective weight loss after bariatric surgery. Since that the human gut microbiota of normal subjects differs between geographic regions, it is possible that rearrangements of the gut microbiota in dysbiosis context are also region-specific. To better understand how gut microbiota contribute to obesity, this study compared the composition of the human gut microbiota of obese and lean people from six different regions and showed that the microbiota compositions in the context of obesity were specific to each studied geographic location. Furthermore, we analyzed the functional patterns using shotgun DNA metagenomic sequencing and compared the results with other obesity-related metagenomic studies, we observed that microbial contribution to functional pathways were country-specific. Nevertheless, our study showed that although microbial composition of obese patients was country-specific, the overall metabolic functions appeared to be the same between countries, indicating that different microbiota components contribute to similar metabolic outcomes to yield functional redundancy. Furthermore, we studied the microbiota functional changes of obese patients after bariatric surgery, by shotgun metagenomics sequencing and observed that changes in functional pathways were specific to the type of obesity treatment. In all, our study provides new insights into the differences and similarities of obese gut microbiota in relation to geographic location and obesity treatments.
Project description:This review provides a literature overview of new findings relating nutritional genomics and bariatric surgery. It also describes the importance of nutritional genomics concepts in personalized bariatric management. It includes a discussion of the potential role bariatric surgery plays in altering the three pillars of nutritional genomics: nutrigenetics, nutrigenomics, and epigenetics. We present studies that show the effect of each patient's genetic and epigenetic variables on the response to surgical weight loss treatment. We include investigations that demonstrate the association of single nucleotide polymorphisms with obesity phenotypes and their influence on weight loss after bariatric surgery. We also present reports on how significant weight loss induced by bariatric surgery impacts telomere length, and we discuss studies on the existence of an epigenetic signature associated with surgery outcomes and specific gene methylation profile, which may help to predict weight loss after a surgical procedure. Finally, we show articles which evidence that bariatric surgery may affect expression of numerous genes involved in different metabolic pathways and consequently induce functional and taxonomic changes in gut microbial communities. The role nutritional genomics plays in responses to weight loss after bariatric surgery is evident. Better understanding of the molecular pathways involved in this process is necessary for successful weight management and maintenance.