Bariatric Surgery: Microbiome & Diabetes

Active, not recruiting

• Conditions: Obesity

• Registration Number: NCT03723486
• Lead Sponsor: University Health Network, Toronto

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2017-11-13
• Study First Submitted QC: 2018-10-25
• Study First Posted: 2018-10-29
• Primary Completion: 2022-06-30
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-01
• Last Update Posted: 2022-11-02
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 120

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).

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in HOMA-IR	Change from Baseline HOMA-IR at 6 months post bariatric surgery	HOMA-IR which represents insulin resistance and is calculated based on (glucose \[mmol/L\] x insulin \[mU/L\] / 22.5).

Secondary Outcome Measures

Name	Time	Method
Stool Sample: 16S sequencing	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Stool sample analysis
Stool Sample: Short Chain fatty acid	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Stool sample analysis
Anthropometry:Height	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Anthropometric height
Questionnaires: Dental questionnaire,	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	General questionnaire
Oral microbiome: Mouth rinse	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Oral sample
Oral microbiome: Oral Plaque	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Oral sample
Stool Sample: qPCR	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Stool sample analysis
Stool Sample: Metagenome.	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Stool sample analysis
Appetite assessment	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Appetite questionnaire
Anthropometry: weight	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Anthropometric weight
Anthropometry: Hip-circumference	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Anthropometric measurements (measured in cm)
Fasting Insulin	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Blood work measurement (measured in pmol/L)
Anthropometry: Waist circumference	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Anthropometric measurements (measured in cm)
Questionnaires: Activity Log	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	General questionnaire
Questionnaires: Food record	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	General questionnaire
Oral microbiome: Tongue plaque	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Oral sample
Glucose	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Blood work measurement (measured mmol/L)
Plasma endotoxin	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Blood work measurement of lipopolysaccharide
Questionnaires: Environmental questionnaire	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	General questionnaire
Oral microbiome: Saliva	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Oral sample
C peptide	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Blood work measurements (measured in pmol/L)
Gut Hormone	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Blood work measurement
HbA1c	4 time points; pre-Optifast (baseline), post-Optifast (at the time of surgery), 1 and 6 months post surgery	Blood work measurements (measured in %)

Trial Locations

Locations (1)

University Health Network, Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada