Clinical trial NCT02893709: Factors Influencing the Human Gut Microbiome Profile in Multi-ethnic Groups of the Singapore Community (FAMES)
Official title: Factors Influencing the Human Gut Microbiome Profile in Multi-ethnic Groups of the Singapore Community (FAMES)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastroesophageal Reflux Disease
Lead sponsor: Changi General Hospital
Sponsor class: OTHER
Collaborators: name: National University of Singapore
name: Universiti Teknologi Mara
First posted: 2016-09-08
Enrollment: 36
Sex: ALL
Minimum age (years): 21
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in species diversity after omeprazole treatment, as measured by diversity indices
timeFrame: 1 week, 2 weeks
measure: Emergence of signature taxa after omeprazole treatment, as measured by indicator value
timeFrame: 1 week, 2 weeks
measure: Differences in species diversity between gender, as measured by diversity indices
timeFrame: Baseline
measure: Differences signature taxa among ethnic groups, as measured by indicator value
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Changi General Hospital
Study officials:
affiliation: Changi General Hospital
name: Tiing Leong Ang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.