Factors Influencing the Human Gut Microbiome Profile in Multi-ethnic Groups of the Singapore Community (FAMES) (FAMES)

The objectives of this study are to examine the effects of ethnicity, gender, and proton pump inhibitor (PPI, omeprazole), on the human gut microbiome. The investigators hypothesize that PPI therapy might perturb microbial communities and alter the gut microbiome. Young, healthy subjects of Chinese, Malay and Indian ancestry, were enrolled. They were required to provide a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for a duration of 7 days. Stool samples were collected again on Day 7 and Day 14 (one week after stopping omeprazole). The DNA samples were subjected to 16S ribosomal ribonucleic acid (rRNA) sequencing.

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: Omeprazole

Detailed Description

Background and Aim: The objectives of this study are to examine the effects of ethnicity, gender, and proton pump inhibitor (PPI, omeprazole), on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. The investigators hypothesize that PPI therapy might perturb microbial communities and alter the gut microbiome.

Methods: Healthy subjects of Chinese (n=12), Malay (n=12) and Indian (n=10) ancestry, aged 21-37 years old, were enrolled. They were required to provide a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for a duration of 7 days. Stool samples were collected again on Day 7 and Day 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples. This was followed by PCR, library construction, 16S rRNA sequencing using Illumina MiSEQ, and statistical and bioinformatics analyses.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 37 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed written informed consent,
2. Aged between 21-35 years of age,
3. Chinese, Malay or Indian ancestry through three generations,
4. Clinical laboratory assessment results within normal limits, unless the deviation is considered not clinically significant by the investigator,
5. Subject is healthy with no clinically significant disease or condition as determined through their medical history, physical examination, and results from clinical laboratory tests that are performed within 2 weeks before the baseline visit at Day 1,
6. Ability to communicate with the investigator and to understand and comply with all requirements of study participation.
7. Female subjects must be in the first half of their menstrual cycle (i.e. 1 to 14 days after the end of the previous menstruation) at Research Study entry.

Exclusion Criteria:

1. Any acute illness within 2 weeks before Day 1, unless otherwise approved by the PI,
2. Presence of chronic illnesses e.g. diabetes, renal disease, gastrointestinal disease, etc., which, in the opinion of the investigator, could compromise the data of the study,
3. Subjects who declare themselves positive for HIV or viral hepatitis (Hepatitis A, B, C),
4. Treatment within the previous 3 months with antibiotics,
5. Treatment with any prescription or over-the-counter (OTC) medications, or herbal supplements within 4 weeks of Day 1 unless approved by the PI,
6. Consumption of probiotics or lactobacillus-containing products e.g. Yakult, Vitagen or Yogurt within 4 weeks of Day 1 unless approved by the PI,
7. Abnormal biochemistry indicators,
8. Poor peripheral venous access,
9. Involvement in the planning or conduct of this study,
10. Irregular bowel habits or complains of constipation problem.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omeprazole; A course of omeprazole at therapeutic dose (20 mg daily) for a duration of 7 days	Drug: Omeprazole; Oral administration of omeprazole at therapeutic dose (20 mg daily) for a duration of 7 days; Other Names: Omezole20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in species diversity after omeprazole treatment, as measured by diversity indices	1 week, 2 weeks
Emergence of signature taxa after omeprazole treatment, as measured by indicator value	1 week, 2 weeks
Differences in species diversity between gender, as measured by diversity indices	Baseline
Differences signature taxa among ethnic groups, as measured by indicator value	Baseline

Collaborators and Investigators

• Sponsor: Changi General Hospital
• Collaborators: National University, Singapore; Universiti Teknologi Mara
• Investigators: Principal Investigator: Tiing Leong Ang, MD, Changi General Hospital

Publications and helpful links

General Publications

• Freedberg DE, Toussaint NC, Chen SP, Ratner AJ, Whittier S, Wang TC, Wang HH, Abrams JA. Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial. Gastroenterology. 2015 Oct;149(4):883-5.e9. doi: 10.1053/j.gastro.2015.06.043. Epub 2015 Jul 9.
• Jackson MA, Goodrich JK, Maxan ME, Freedberg DE, Abrams JA, Poole AC, Sutter JL, Welter D, Ley RE, Bell JT, Spector TD, Steves CJ. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016 May;65(5):749-56. doi: 10.1136/gutjnl-2015-310861. Epub 2015 Dec 30.
• Clooney AG, Bernstein CN, Leslie WD, Vagianos K, Sargent M, Laserna-Mendieta EJ, Claesson MJ, Targownik LE. A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors. Aliment Pharmacol Ther. 2016 May;43(9):974-84. doi: 10.1111/apt.13568. Epub 2016 Feb 29.
• Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L, Tigchelaar EF, Jankipersadsing SA, Cenit MC, Harmsen HJ, Dijkstra G, Franke L, Xavier RJ, Jonkers D, Wijmenga C, Weersma RK, Zhernakova A. Proton pump inhibitors affect the gut microbiome. Gut. 2016 May;65(5):740-8. doi: 10.1136/gutjnl-2015-310376. Epub 2015 Dec 9.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: August 24, 2016
• First Submitted That Met QC Criteria: September 3, 2016
• First Posted (Estimate): September 8, 2016

Study Record Updates

• Last Update Posted (Estimate): September 8, 2016
• Last Update Submitted That Met QC Criteria: September 3, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: FAMES

Plan for Individual participant data (IPD)

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