An Intervention on Healthy Adults of Probiotics on Gut Flora Metabolisms of Choline

Probiotics Intervention on Gut Flora Metabolisms of Choline:A Randomized Double-Blind Control Trial

The aim of the study is to examine the effects of probiotics intervention on choline metabolites and intestinal microbiota composition using a randomized double blind clinical trial. Also, we proposed to explore the real-time change of choline metabolites after probiotics intervention through a PC challenge test. Our study will clarify the biochemical pathway involved in metabolic diseases and hope to provide a new targeted-preventive and therapeutic strategy for chronic metabolic diseases.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: probiotics intervention; Dietary supplement: non-probiotic control

Detailed Description

Dietary choline (mainly refer to phosphatidylcholine, PC) produce trimethylamine (TMA) through the action of gut flora in vivo. TMA then readily absorbed into systemic circulation and oxidized by hepatic flavin monoxygenases (FMO3) to trimethylamine-N-oxide (TMAO). The elevated levels of circulating TMAO is identified as a risk factor for the prevalence and development of metabolic diseases such as cardiovascular diseases and nonalcoholic fatty liver diseases. Targeting gut flora for reducing TMAO may be a promising approach for preventing chronic metabolic diseases. Recent studies found that some strains representing two different phyla (Firmicutes and Proteobacteria) are capable of producing TMA from choline in vitro. On the other hand, TMA intervention can change the structure of intestinal flora, reducing the abundance of bifidobacterium and lactobacillus. Probiotics can improve the ecological balance of the gut flora, which might be beneficial to human health and disease prevention. However, whether probiotics could inhibit the TMA-producing bacterias and reduce the TMA and TMAO levels through balancing the gut flora was unclear.

In order to explore whether probiotics can reduce the TMA and TMAO levels, we are proposed to recruit 50 volunteers aged from 18-30 years old to participate in the randomized double-blind trial. The volunteers are randomized allocated into different intervention groups. The probiotics intervention group is provided once daily orally-taken powder in a sachet, which contains 4 strains of probiotics. The non-probiotic control is provided with a powder without probiotics , but has same look, color, taste, flavor and weight as the probiotics intervention group. A PC challenge test will be hold before and after the 4 weeks intervention. The blood and fecal sample will be collected before and after the trial and analyzed by appropriate method. The dietary assessment is assessed by a 3-day dietary record.The statistic analysis is by SPSS 23.0.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • SunYat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males at 18 to 30 years old;
• Free from antibiotics and probiotic products for at least 1 month;
• Willing to participate in the study, consume the test product and perform all measurements.

Exclusion Criteria:

• Sever physical diseases;
• Intolerance to probiotics or eggs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: probiotics intervention; The probiotic is provided in sachets as a 2g powder dried with corn starch.; The powder is orally taken once daily for 4 weeks.; The powder contains totally 11 log 10 colony forming units(CFU) of probiotics.; The types of probiotics are Lactobacillus.rhamnosus, Lactobacillus.acidophilus, Bifidobacteria.animalis and Bifidobacteria.longum.	Dietary supplement: probiotics intervention; The probiotics intention is provided with 4 strains of probiotics as a 2g sachet powder, dried with corn starch for 4 weeks.
PLACEBO_COMPARATOR: non-probiotic control; The placebo is corn starch alone provided and the shape, color, weight,flavor and taste are same with the powder of probiotics intervention.	Dietary supplement: non-probiotic control; The placebo is corn starch alone provided and the shape, color, flavor and taste are same with the powder of probiotics intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
choline metabolites	The metabolites of choline before and after the intervention including free choline, betaine, TMA, TMAO will be measured by UPLC/MS.	4 weeks later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intestinal microbiota composition	The intestinal microbiota composition of feces before and after the intervention will be examined by 16S-DNA.	4 weeks later
anthropometry measurement	The height and weight which are combined to report BMI in kg/m^2 will be measured before and after the intervention by professional investigators.	4 weeks later
blood biochemical markers	Overnight fasting serum total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDLc), HDL cholesterol (HDLc) and fasting blood glucose were measured by colorimetric methods using a Hitachi 7600-010 automated analyzer.	4 weeks later

Collaborators and Investigators

• Sponsor: Huilian Zhu
• Investigators: Study Chair: Zhu Hui lian, Professor, Sun Yat-sen University

Publications and helpful links

General Publications

• Chen S, Jiang PP, Yu D, Liao GC, Wu SL, Fang AP, Chen PY, Wang XY, Luo Y, Long JA, Zhong RH, Liu ZY, Li CL, Zhang DM, Zhu HL. Effects of probiotic supplementation on serum trimethylamine-N-oxide level and gut microbiota composition in young males: a double-blinded randomized controlled trial. Eur J Nutr. 2021 Mar;60(2):747-758. doi: 10.1007/s00394-020-02278-1. Epub 2020 May 21.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ACTUAL): December 31, 2018

Study Registration Dates

• First Submitted: September 19, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (ACTUAL): September 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: DIC2016-08

Drug and device information, study documents

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