Investigating the Gut Microbiota Modulation Effects of Allicin for Cardiovascular Disease Protection and Establishing Microbiota Directed Personalized Nutrition Guidance With Novel Humanized Gnotobiotic Mice Model, Microbial Culturomics and Metabolomic Technique

Investigators recruited 10 trimethylamine N-oxide (TMAO) producers to test the effect of garlic juice containing allicin on gut microbiota modulation and TMAO production.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Dietary supplement: Raw garlic juice containing allicin

Detailed Description

Trimethylamine N-oxide (TMAO) was recently discovered as a novel and independent risk factor for promoting atherosclerosis while it is generated from dietary carnitine through the metabolism of gut microbiota for decades. Allicin, the major compound in raw garlic juice, is a naturally antimicrobial phytochemical found in raw garlic juice and easily acquired from the diet. Investigators' previous study suggests dietary allicin reduces the transformation of L-carnitine to TMAO through the impact on gut microbiota in mice. Therefore, it is worth investigating whether raw garlic juice intake could reduce the TMAO productivity of human gut microbiota as well as modulate gut microflora. Investigators plan to recruit 10 TMAO producers to receive garlic juice for one week. The plasma and urine TMAO concentration will be measured by the LC-MS, and the gut microbiota composition will be analyzed by the next-generation sequencing, through bioinformatics analysis. Investigators expected after intake garlic juice for one week, it could prevent the cardiovascular disease risk via gut microbiota modulation and reduction of plasma and urine TMAO.

Screening of the TMAO producer:

The healthy participants were recruited, the criteria as follows: (1) age ≥ 20 years old; (2) no exposure to antibiotics, probiotics, or carnitine supplements within the previous month; (3) have no history of chronic diseases including, diabetes mellitus, myasthenia gravis, chronic renal disease, hyperparathyroidism, epilepsy, and severe anemia; (4) Participants were excluded from the study if they reported recent gastrointestinal discomfort (such as abdominal pain or diarrhea). To screening the TMAO producer, Investigators use the oral carnitine challenge test (OCCT) method which previously exhibited better efficacy than fasting plasma TMAO to identify the TMAO producer phenotype. All of the participants fasted at least 8 hours before performing OCCT. 1500 mg of L-carnitine (3 tablets, General Nutrition Centers, Inc., USA) orally administrated to the participants. The blood and urine of participants were collected at 0, 24, 48, and 72 hours after carnitine intake. Participants with plasma TMAO ≧ 10 μM after OCCT were defined as high TMAO producers and proceeded into the garlic juice intervention test.

Garlic Juice Intervention:

High-TMAO producers asked to consume 55 mL of raw garlic juice (48 mg of allicin equivalent) once a day during dinner for one week. High-TMAO producers suggested consuming the garlic juice with a meal. The high-TMAO producers were free to choose their diet, no restriction on the type of food. After one week of raw garlic juice intervention, the second OCCT was performed.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 20-65 years old
• Healthy subjects with TMAO producing ability

Exclusion Criteria:

• Exposure to antibiotics, probiotics, or carnitine supplements within the previous month
• Have a history of chronic diseases including, diabetes mellitus, myasthenia gravis, chronic renal disease, hyperparathyroidism, epilepsy, and severe anemia
• Have gastrointestinal discomfort (such as abdominal pain or diarrhea)

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: Raw garlic juice; Raw garlic juice treatment group	Dietary supplement: Raw garlic juice containing allicin; Fresh garlic juice containing around 48mg allicin for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and urine TMAO level (ppm)	Quantitation of plasma and urine TMAO level by LC-MS	6 months
Compositional analysis of gut microbiota (% of different bacteria species)	Next-generation sequencing and bioinformatics	6 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Actual): May 18, 2019
• Study Completion (Actual): May 18, 2019

Study Registration Dates

• First Submitted: September 6, 2020
• First Submitted That Met QC Criteria: September 6, 2020
• First Posted (Actual): September 11, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Protective Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antioxidants; Free Radical Scavengers; Allicin
• Other Study ID Numbers: 201712031RIND

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No