The long term effect of metabolic profile and microbiota status in early gastric cancer patients after subtotal gastrectomy
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PROVIDER: PRJEB28412 | ENA |
REPOSITORIES: ENA
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Project description:Gastric acidity is essential for the function of the human stomach. pH homeostasis is facilitated by gastrin, a hormone secreted from the gastric antrum in response to a rise in pH, leading to acid secretion from the gastric corpus. Sleeve gastrectomy (SG), a bariatric surgery in which 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. We used histology and single-cell RNA sequencing to study the gastric antrum and corpus epithelium of naïve patients, and of patients who underwent SG years earlier. SG was associated with an increase in a sub-population of acid-secreting parietal cells which overexpress respiratory enzymes and carbonic anhydrase, and an increase in the fraction of histamine-secreting enterochromaffin-like cells (ECLs). Notably, ECLs of SG-operated patients over-expressed genes coding for biosynthesis of neuropeptides and of serotonin. Mathematical modeling of pH homeostasis by gastrin showed that fasting pH is not sensitive to nearly all model parameters. Robustness is a result of the ability of gastrin to induce acid secretion as well as increase the number of ECLs and parietal cells, a feedback analogous to a non-linear proportional and integral feedback control, that drives adaptation of the epithelium to acid-secretion demand. Quantitative predictions of the model on the gastric response to SG were validated in patients: SG induced a 5-fold increase in blood gastrin levels as early as one day post-surgery, and an over 30% increase in the number of parietal cells and ECLs per gland years after surgery. Together, these empirical and modeling data demonstrate how the human gastric epithelium remodels following SG at the molecular and cellular levels, and more generally how trophic hormones such as gastrin enable robust adaptation of tissue function to meet physiological demand.
2024-12-15 | GSE263018 | GEO
Project description:The long term microbiota and metabolic status in patients with colorectal cancer after curative colon surgery
| PRJEB32249 | ENA
Project description:<p><strong>INTRODUCTION:</strong> Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported.</p><p><strong>OBJECTIVES:</strong> The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities.</p><p><strong>METHODS:</strong> Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis.</p><p><strong>RESULTS:</strong> Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB.</p><p><strong>CONCLUSION:</strong> These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.</p>
2022-03-17 | MTBLS2472 | MetaboLights
Project description:Gastric bypass surgery has proven to be the most effective treatment in controlling hyperglycemia in severely obese patients with diabetes. Here we show that FGF19, a gut hormone, is rapidly induced by bypass surgery in rodents and humans. Administration of FGF19 achieves remission of diabetes through mechanisms beyond weight loss in animal models of diabetes, supporting a role of FGF19 as part of hormonal changes that influence metabolism following surgery. Through an unbiased phenotypic screen in diabetic mice, we identified selective, safe and effective FGF19 analogues. Unexpectedly, FGF19 analogue failed to correct hyperglycemia in patients with type 2 diabetes. In contrast, administration of FGF19 analogue resulted in rapid, robust and sustained improvement in liver fat content and histology in patients with non-alcoholic steatohepatitis, faithfully replicating effect of the surgery. Thus, our work identifies a strategy of replacing gastric bypass surgery by equally effective, but less invasive, treatment for non-alcoholic steatohepatitis. We used microarrays to detail the global programme of gene expression affected by gastric bypass surgery in rats.
2021-09-25 | GSE120530 | GEO
Project description:There is evidence that gastrointestinal operations for non weight-losing purposes are beneficial for diabetes mellitus. Aiming to analyze such hypothesis, patients submitted to gastric bypass for morbid obesity, gastrectomy for gastric cancer and colectomy for colo-rectal cancer will be compared. The end point will be changes in fasting blood glucose and hemoglobin A1c concentration.
| 2119210 | ecrin-mdr-crc
Project description:The Glucagon-Like Peptide-1 (GLP-1) is a proglucagon-derived peptide with regulatory effects on many tissues, including the pancreas, stomach, liver, brain and heart. The rapid inactivation of intestinally secreted GLP-1 by DPP-4 enzyme raises the question of its production in proximity of its targets. Here we show some epithelial cells producing GLP-1 in the stomach of rats and humans. These cells respond specifically to intragastric load of glucose by increasing GLP-1 levels in the portal vein, in vivo in the rat. GLP-1 is known as an incretin, it decreases blood glucose levels after a meal by increasing insulin secretion in response to glucose. The increased GLP-1 secretion in obese individuals who have undergone bariatric surgery is considered as a keystone in the glycemic improvement observed in those patients. Here we show that obese rats that underwent RYGB or VSG exhibit a new gastric mucosa phenotype with expansion and hyperplasia of the mucus neck cells, and increased density of gastric GLP-1 expressing cells compared to sham animals. These findings highlight a potential role of stomach-derived GLP-1 in the outcomes of bariatric surgeries and raise the question of its role in physiology and metabolism.
2020-12-04 | PXD009867 | Pride
Project description:Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) but also up to one year after the intervention by using untargeted metabolomics. 132 serum samples taken from 44 patients before surgery, after hospital discharge (1–3 weeks after surgery) and at a 1-year follow-up during a prospective study (NCT01271062) performed at two study centers (Austria and Switzerland). The samples included 24 patients with type 2 diabetes at baseline, thereof 9 with diabetes remission after one year. The samples were analyzed by using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS, HILIC-QExactive). Raw data was processed with XCMS and drift-corrected through quantile regression based on quality controls. 177 relevant metabolic features were selected through Random Forests and univariate testing and 36 metabolites were identified. Identified metabolites included trimethylamine-N-oxide, alanine, phenylalanine and indoxyl-sulfate which are known markers for cardiovascular risk. In addition we found a significant decrease in alanine after one year in the group of patients with diabetes remission relative to non-remission. Our analysis highlights the importance of assessing multiple points in time in subjects undergoing bariatric surgery to enable the identification of biomarkers for treatment response, cardiovascular benefit and diabetes remission. Key-findings include different trend pattern over time for various metabolites and demonstrated that short term changes should not necessarily be used to identify important long term effects of bariatric surgery.
2015-09-15 | MTBLS218 | MetaboLights
Project description:In order to identify mechanisms underlying the long-term beneficial effect of bariatric surgery on abdominal subcutaneous WAT, we performed gene microarray analyses on adipose tissue from a cohort of obese women. Adipose tissue biopsies were obtained before RYGB, and then 2 and 5 years thereafter. To evaluate the long-term effect of Roux-en-Y gastric bypass (RYGB) surgery on WAT, we also compared the WAT gene expression at 5 years postsurgery with that of age-matched nonoperated women.
2022-04-28 | GSE199063 | GEO
Project description:Sequencing of 16S ribosomal RNA (rRNA) gene, which has improved the characterization of microbial community, has made it possible to detect a low level Helicobacter pylori (HP) sequences even in HP-negative subjects which were determined by a combination of conventional methods. This study was conducted to obtain a cutoff value for HP colonization in gastric mucosa biopsies and gastric juices by the pyrosequencing method. Corresponding author: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea (Tel., +82-31-787-7008; e-mail, nayoungkim49@empas.com). Microbial DNA from gastric mucosal samples [gastric antrum (n=63, mucosal biopsy), follow-up sample on gastric antrum (n=16, mucosal biopsy), and gastric body (n=18, mucosal biopsy)] and gastric juices (n=4, not mucosal biopsy) was amplified by nested PCR using universal bacterial primers, and the 16S rRNA genes were pyrosequenced.
2014-09-18 | E-GEOD-61493 | biostudies-arrayexpress
Project description:Whether there are subsequent changes of metabolic profiles and microbiota status after partial colectomy remains unknown. We evaluated and compared long-term effects of microbiota status and metabolic profiles in early colorectal cancer (CRC) patients after curative colectomy to the controls. In this cross-sectional study, we analyzed metabolic syndrome occurrence in 165 patients after curative partial colectomy with right hemicolectomy (RH) or low anterior resection (LAR) and 333 age-sex matched controls. Fecal samples from some of those with RH, LAR, and controls were analyzed by next-generation sequencing method. The occurrences of metabolic syndrome were significantly higher in patients after RH, but not LAR, when compared with the controls over the long term (> 5 years) follow-up (P = 0.020). Compared with control group, RH group showed lower bacterial diversity (P = 0.007), whereas LAR group showed significantly higher bacterial diversity at the genera level (P = 0.016). Compared with the control group, the principal component analysis revealed significant differences in bacterial genera abundance after RH and LAR (P < 0.001). Furthermore, the Firmicutes to Bacteroidetes ratio was significantly lower in the RH group than the control group (22.0% versus 49.4%, P < 0.05). In conclusion, early CRC patients after RH but not LAR were associated with a higher occurrence of metabolic syndrome than the controls during long-term follow-up. In parallel with metabolic change, patients with RH showed dysbiosis with a tendency to decreased richness and a significant decrease in the diversity of gut microbiota.
| S-EPMC6570030 | biostudies-literature