Clinical trial NCT05980884: Using Gut Microbial Gbu Gene Testing to Estimate Host TMAO Production Capacity
Official title: Evaluation of Microbial-derived TMAO Production From Carnitine Intake by Testing Fecal Gbu Gene
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gut Dysbiosis for TMAO Production From L-carnitine Consumption
Keywords: gbu gene cluster
TMAO
gut microbiota
red meat
cardiovascular disease
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2023-08-08
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The risk of cardiovascular diseases from red meat consumption varies among individuals due to variations in gut microbiota. L-carnitine in red meat can be converted to TMAO in the body by certain bacteria. Not everyone experiences a significant increase in TMAO levels after consuming carnitine. Gut microbiota differences are observed between high and low TMAO producers. The presence of the gbu gene in gut microbiota is linked to TMAO production. This clinical research aims to determine if the gbu gene can predict TMAO levels after dietary carnitine intake.

Detailed description: The risk of developing cardiovascular diseases due to the consumption of red meat varies among individuals, and this may be attributed to differences in the composition and function of gut microbiota. Studies have found that red meat, rich in L-carnitine, may be metabolized by certain anaerobic bacteria in the intestines to produce trimethylamine N-oxide (TMAO) in the human body. Previous research utilizing the oral carnitine challenge test (OCCT) revealed that not everyone experiences a significant increase in blood TMAO levels after consuming carnitine. Moreover, individuals with high TMAO production and low TMAO production showed distinct differences in their gut microbiota.

Furthermore, we have discovered a significant correlation between the abundance of the gbu gene in gut microbiota and the production of TMAO in response to dietary carnitine intake. Therefore, through the design of clinical research, we aim to investigate and assess whether the abundance of the gbu gene in gut microbiota can predict the levels of TMAO produced in the human body under dietary carnitine intake.

Eligibility criteria: Inclusion Criteria:

* Adult with age between 18 to 70
* Must be able to swallow tablets

Exclusion Criteria:

* Antibiotics use within one month
* L-carnitine supplement use within one month
* Chronic diarrhea
* Myasthenia gravis
* Diabetes mellitus
* Parathyroid disorders
* Chronic kidney disease
* Epilepsy
* Severe anemia
* Cardiovascular diseases.

Primary outcomes:
measure: Blood TMAO level measured by LC-MS/MS
timeFrame: up to 7-10 days
measure: Urine TMAO level measured by LC-MS/MS
timeFrame: up to 7-10 days
measure: Fecal gbuB gene abundance measured by qPCR
timeFrame: up to 7-10 days
Secondary outcomes:
measure: Carnitine intake measured by 24hr dietary record
timeFrame: up to 7-10 days
measure: Gut microbiome profiles measured by shotgun metagenome sequencing
timeFrame: up to 7-10 days
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References:
citation: Wu WK, Lo YL, Chiu JY, Hsu CL, Lo IH, Panyod S, Liao YC, Chiu THT, Yang YT, Kuo HC, Zou HB, Chen YH, Chuang HL, Yen JJY, Wang JT, Chiu HM, Hsu CC, Kuo CH, Sheen LY, Kao HL, Wu MS. Gut microbes with the gbu genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition. Gut Microbes. 2025 Dec;17(1):2446374. doi: 10.1080/19490976.2024.2446374. Epub 2024 Dec 26.