Fecal metabolism of obese patients with type 2 diabetes undergoing gastric bypass in Y-Roux (DGYR) with emphasis on bile acids

Author(s)

Camila de Siqueira Cardinelli

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2019-08-12

Examining board members

Dan Linetzky Waitzberg; Claudia Cristina Alves Pereira

• Advisor: Dan Linetzky Waitzberg

Abstract

Bariatric surgery (BS) is an effective method to promote sustained weight loss. Roux-en-Y gastric bypass (RYGB) is highly indicated to severe obesity, especially due to its positive impact on metabolic complications like type 2 diabetes (T2D). Although the high rates of remission or improvements, the mechanisms by which RYGB influences glycemia are still not fully recognized. Therefore, bile acids (BAs) are being pointed as determinant factors, especially due to its potent action on systemic metabolism. BAs act as metabolic regulators by mediating signaling of several process, including substrate utilization in different organs. Thus, increased levels of plasma BAs - frequently observed after RYGB - could promote important metabolic alterations and contribute to glucose homeostasis. Increased plasma BAs is followed by alterations of fecal excretion, as was previously demonstrated by experimental studies. Nowadays, little is known about fecal global metabolomics and its BAs profile in human beings subjected to RYGB, as well as its influence on T2D remission. Our hypothesis considers that RYGB alters metabolomic and BAs profile of obese women with T2D and this could be related to postoperative glucose homeostasis. We recruited 20 obese women with T2D, candidates to RYGB, under attendance on the Digestive Surgery Department of Hospital das Clínicas, School of Medicine - University of São Paulo. Fecal samples were collected before, 3 and 12 months after RYGB. Patients were classified as responsive (R) and nonresponsive (NR) to T2D improvement, according the American Diabetes Association (ADA). Clinical and biochemical variables were also evaluated. Fecal samples were evaluated by: (1) untargeted metabolomic analysis, by using liquid chromatography gas spectrometry (LC-MS) (n=10), in order to determine global metabolomics profile; and (2) targeted metabolomic analysis by Biocrates® (Innsbruck, Áustria) to quantify BAs profile by tandem LC-MS. MetIDQTM software was applied to export data. Statistical analysis included supervised principal component analysis PLS-DA, by Pirouette 3:11 and the online platform MetaboAnalyst 3.0. Different statistical methods were applied: ANOVA, Fold change, teste t student, Wilcoxon and Mann Whitney, to identify diferences of fecal BAs concentrations before and after RYGB. Results indicate that RYGB induced improvement of clinical and biochemical variables in all patients, although glycemic levels were significantly lower on R group. Global metabolomic profile was altered, presenting a significant reduction of 10 fecal BAs after RYGB (p <= 0,05). Changes on postoperative BAs profile were different between R and NR, with a significant decrease of BAs sub fractions on R group, including a significant change on cholic acid (CA) and chenodeoxycholic acid (CDCA) temporal behavior. This reflected on the CA/CDCA ratio and tauroursodeoxycholic acid (TUDCA) between groups ( <=0,05 ). Patients subjected to cholecystectomy (COLE), showed a distinct pattern of BAs profile in comparison with non cholecystectomized patients (NOCOLE). We concluded that RYGB promote fecal metabolomic alterations, followed by a significant reduction of BAs. This reduction was distinctive between R and NR and COLE and NOCOLE patients (AU)

• FAPESP's process: 14/05220-1 - Metabolomics of fecal water in obese patients with Type 2 Diabetes before and after gastroplasty reduction in Y-Roux (GRYR)
• Grantee: Camila de Siqueira Cardinelli
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)