The Association Between Microbiota, Endotoxaemia and the Host Obesity/ Insulin Resistance (MiPOOP Study) (MiPOOP)

The objectives of this study are to examine the effects of ethnicity, central obesity and dietary components, on the human gut microbiome. The investigators hypothesize that these factors have an influence on the composition of the gut microbiome. Healthy subjects (n=35) provided stool samples for gut microbiome profiling using 16S rRNA sequencing and completed a dietary questionnaire. The serum samples were assayed for a panel of inflammatory cytokines. Their associations with central obesity were examined.

Study Overview

• Status: Completed
• Conditions: Central Obesity

Detailed Description

Introduction: Perturbance in the composition of human gut microbiota has been associated with metabolic disorders such as obesity, diabetes mellitus and insulin resistance. The objectives of this study are to examine the effects of ethnicity, central obesity and dietary components, on the human gut microbiome. The investigators hypothesize that these factors have an influence on the composition of the gut microbiome.

Methods: Subjects of Chinese (n=14), Malay (n=10) or Indian (n=11) ancestry, median age 39 (range:22-70 years old), were enrolled. The subjects provided stool samples for gut microbiome profiling using 16S rRNA sequencing and completed a dietary questionnaire. The serum samples were assayed for a panel of biomarkers (Interleukin-6, tumour necrosis factor alpha, adiponectin, cleaved cytokeratin 18, lipopolysaccharide binding protein and limulus amebocyte lysate). Central obesity was defined by waist circumference cut-offs in Asians.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 529889
    • Changi General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers recruited through advertisement or patients with type 2 diabetes mellitus from hospital records.

Description

Inclusion Criteria:

• Provision of signed written informed consent,
• Aged between 21- 75 years old,
• Body Mass Index (BMI) of > 18 kg/m2,
• Ethnic group of either Chinese, Malay or Indian as evidenced by identification card,
• Subject with absence of impaired glucose tolerance,
• Subject is healthy with no clinically significant disease or condition as determined through their medical history, physical examination; Diabetes mellitus was defined as Type 2 DM fulfilling the WHO criteria and the care of Department of Endocrinology, Changi General Hospital,
• Ability to communicate with investigator and to understand and comply with all requirements of study participation.

Exclusion Criteria:

• Subject who are viral Hepatitis (B or C) or HIV positive as per declaration,
• Subject who had bariatric surgery including lap banding, gastric sleeve surgery, cholecystectomy,
• Subject who has > 5% weight loss in the last 3 months prior to study enrolment as per declaration,
• Subject who are on 'stable' insulin sensitizers such as such as rosiglitazone, metformin for the last 3 months prior to enrolment,
• Pregnant women,
• Subject who has been treated with antibiotics within 6 weeks of enrolment,
• Subject who has usage of lactulose, dietary fibres for purpose of constipation,
• Subject with immune-compromised status; undergoing chemotherapy, on steroid,
• Subject with FMHx or PMHx of autoimmune disease, GI cancers, inflammatory bowel disease, Irritable bowel syndrome and anxiety or depression as per declaration.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Central obesity; Cases with central obesity as defined by waist circumference cut-offs ≥ 90 cm in men and ≥ 80 cm in women for Asians
No central obesity; Controls with no central obesity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of human gut microbiome profile with central obesity and dietary pattern	Species diversity as measured by diversity indices	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of human gut microbiome profile with ethnicity	Species diversity as measured by diversity indices	1 day
Association of interleukin-6 with central obesity and microbiota	Interleukin-6 concentration in pg/ml	1 day
Association of tumour necrosis factor - alpha with central obesity and microbiota	Tumour necrosis factor - alpha concentration in pg/ml	1 day
Association of cleaved cytokeratin 18 with central obesity and microbiota	Cleaved cytokeratin 18 concentration in units/L	1 day
Association of limulus amebocyte lysate with central obesity and microbiota	Limulus amebocyte lysate concentration in EU/ml	1 day
Association of lipopolysaccharide binding protein with central obesity and microbiota	Lipopolysaccharide binding protein concentration in ng/ml	1 day
Analysis of dietary components based on recommended daily allowance	Dietary questionnaire	3 days

Collaborators and Investigators

• Sponsor: Changi General Hospital
• Collaborators: Genome Institute of Singapore, A*Star
• Investigators: Principal Investigator: John Chen Hsiang, MD, PhD, Changi General Hospital

Publications and helpful links

General Publications

• Hsiang JC, Bai WW, Raos Z, Stableforth W, Upton A, Selvaratnam S, Gane EJ, Gerred SJ. Epidemiology, disease burden and outcomes of cirrhosis in a large secondary care hospital in South Auckland, New Zealand. Intern Med J. 2015 Feb;45(2):160-9. doi: 10.1111/imj.12624.
• Ho EXP, Cheung CMG, Sim S, Chu CW, Wilm A, Lin CB, Mathur R, Wong D, Chan CM, Bhagarva M, Laude A, Lim TH, Wong TY, Cheng CY, Davila S, Hibberd M. Human pharyngeal microbiota in age-related macular degeneration. PLoS One. 2018 Aug 8;13(8):e0201768. doi: 10.1371/journal.pone.0201768. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2016
• Primary Completion (Actual): September 26, 2017
• Study Completion (Actual): September 26, 2017

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 8, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: September 8, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: metabolic syndrome; ethnicity; gastrointestinal microbiome; dietary components
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Sepsis; Hyperinsulinism; Bacteremia; Toxemia; Obesity; Insulin Resistance; Endotoxemia; Obesity, Abdominal
• Other Study ID Numbers: MiPOOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No