Bariatric Surgery: Microbiome & Diabetes

Obesity Clinical Trial

Official title:

Changes in the Intestinal and Oral Microbiome of Morbidly Obese Patients Undergoing Gastric Bypass Surgery in Relation to Insulin Resistance and Metabolic Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03723486
• Other study ID #: 15-8784-AE
• Secondary ID: TB2-138775
• Status: Active, not recruiting
• Start date: November 2015
• Est. completion date: December 30, 2023

Study information

• Verified date: November 2022
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is a prospective cohort study, following 80 morbidly obese patients undergoing bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB). The investigators are measuring intestinal microbiota (IM) and oral microbiota (OM) at the beginning before any treatment, at the time of surgery, which is after a very low calorie standard diet, and 1 and 6 months after surgery. The investigators assess whether changes in IM are related to changes in insulin resistance (IR), other features of the metabolic syndrome (MetS) and OM.

Description:

Morbid obesity is associated with not only type 2 diabetes (T2D) of morbidly obese patients), but also cardiovascular complications, all of which remarkably improved and even resolved with bariatric surgery, of which the RYGB surgery has become the gold standard. Many studies have shown that within a few weeks post-RYGB there is dramatic improvement in IR and/or T2D independent of weight loss that ensues. These results led us to hypothesize that changes in intestinal microbiome (IM) composition and metagenome may be independently associated with improvement in metabolic parameters in humans undergoing RYGB.

Another aspect of RYGB that has not been studied is the potential changes in oral microbiome (OM) and salivary proteome (SP) and their relationship with weight loss and metabolic improvement. Understanding the OM and SP in morbidly obese patients before and after RYGB is important because shifts in the OM and SP may explain the susceptibility of these patients for oral infections like periodontal disease, which is more prevalent and severe in this population, particularly if T2D is present To our knowledge there are no longitudinal studies the relation between oral and intestinal microbiome before and after bariatric surgery. Furthermore, there are no studies looking at the effect of weight-reduction with the very low calorie diet (VLCD) Optifast regimen on IM, which the investigators plan to do. As IM may contribute to obesity and IR/T2D, the latter being the most dominant feature of the MetS. However, whether specific IM compositions are associated with improvement of obesity, IR/T2D and other features of the MetS is not clear; and the effects of RYGB on IM for treatment of these disorders in morbid obesity have not been well studied.

The investigators will conduct a prospective observational study of morbidly obese patients undergoing RYGB, in which the investigators will measure the intestinal microbiome before and after surgery along with insulin resistance and metabolic syndrome. Baseline measurements will be done before the pre-operative run-in with the very low calorie Optifast regimen (800 kcal/d) given before the laparoscopic RYGB (1 week/100 lbs body weight) to reduce the liver size for surgical access. Preoperatively, Optifast likely leads to changes in IM (never assessed) in addition to weight loss and improvement in MetS parameters. Aim: To track the changes in IM structure and function (metagenome) of morbidly obese patients undergoing laparoscopic RYGB through 3 stages - a) before vs. after pre-op Optifast weight reduction treatment 24; and post-op RYGB at b) 1 month; and at c) 6 months. The investigators will correlate the specific changes in IM through these stages, to improvement in IR and other features of the MetS. At the same time points the investigators will also measure the OM, salivary flow rate and SP, as well as oral inflammatory load.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: December 30, 2023
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Morbidly obese patients (BMI > 40 kg/m2 or BMI >35-40 kg/m2 with other severe weight loss responsive comorbidities, undergoing laparoscopic RYGB surgery).

Exclusion Criteria:

• regular intake of non-steroidal anti-inflammatory drugs; prebiotics, probiotics or antibiotics or any experimental drug in the 3 months prior to study entry; type 1 diabetes, chronic gastrointestinal diseases, previous gastrointestinal surgery modifying the anatomy, smoking; pregnancy or breastfeeding; patients not tolerating Optifast; bariatric surgery other than RYGB patients.

Related Conditions & MeSH terms

• Insulin Resistance
• Metabolic Syndrome
• Obesity

Locations

Country	Name	City	State
Canada	University Health Network, Toronto General Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

References & Publications (7)

Arimatsu K, Yamada H, Miyazawa H, Minagawa T, Nakajima M, Ryder MI, Gotoh K, Motooka D, Nakamura S, Iida T, Yamazaki K. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep. 2014 May 6;4:4828. doi: 10.1038/srep04828. — View Citation

Chaffee BW, Weston SJ. Association between chronic periodontal disease and obesity: a systematic review and meta-analysis. J Periodontol. 2010 Dec;81(12):1708-24. doi: 10.1902/jop.2010.100321. Epub 2010 Aug 19. Review. — View Citation

Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, Xu A, Chavakis T, Bornstein AB, Ehrhart-Bornstein M, Lamounier-Zepter V, Lohmann T, Wolf T, Bornstein SR. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013 Dec;13(6):514-22. doi: 10.1038/tpj.2012.43. Epub 2012 Oct 2. — View Citation

Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jørgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clément K, Doré J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T; MetaHIT consortium, Bork P, Wang J, Ehrlich SD, Pedersen O. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013 Aug 29;500(7464):541-6. doi: 10.1038/nature12506. — View Citation

Lewis MC, Phillips ML, Slavotinek JP, Kow L, Thompson CH, Toouli J. Change in liver size and fat content after treatment with Optifast very low calorie diet. Obes Surg. 2006 Jun;16(6):697-701. — View Citation

Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2014 Feb;2(2):152-64. doi: 10.1016/S2213-8587(13)70218-3. Epub 2014 Feb 3. — View Citation

Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012 Oct 4;490(7418):55-60. doi: 10.1038/nature11450. Epub 2012 Sep 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HOMA-IR	HOMA-IR which represents insulin resistance and is calculated based on (glucose [mmol/L] x insulin [mU/L] / 22.5).	Change from Baseline HOMA-IR at 6 months post bariatric surgery
Secondary	Stool Sample: 16S sequencing	Stool sample analysis	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Stool Sample: qPCR	Stool sample analysis	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Stool Sample: Short Chain fatty acid	Stool sample analysis	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Stool Sample: Metagenome.	Stool sample analysis	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Appetite assessment	Appetite questionnaire	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Anthropometry:Height	Anthropometric height	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Anthropometry: weight	Anthropometric weight	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Anthropometry: Waist circumference	Anthropometric measurements (measured in cm)	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Anthropometry: Hip-circumference	Anthropometric measurements (measured in cm)	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Questionnaires: Food record	General questionnaire	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Questionnaires: Activity Log	General questionnaire	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Questionnaires: Environmental questionnaire	General questionnaire	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Questionnaires: Dental questionnaire,	General questionnaire	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Oral microbiome: Saliva	Oral sample	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Oral microbiome: Mouth rinse	Oral sample	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Oral microbiome: Oral Plaque	Oral sample	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Oral microbiome: Tongue plaque	Oral sample	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	C peptide	Blood work measurements (measured in pmol/L)	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	HbA1c	Blood work measurements (measured in %)	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Glucose	Blood work measurement (measured mmol/L)	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Fasting Insulin	Blood work measurement (measured in pmol/L)	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Plasma endotoxin	Blood work measurement of lipopolysaccharide	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery
Secondary	Gut Hormone	Blood work measurement	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery