Identification of TMAO-producer phenotype and host–diet–gut dysbiosis by carnitine challenge test in human and germ-free mice

Wu, Wei-Kai; Chen, Chieh‐Chang; Liu, Po-Yu; Panyod, Suraphan; Liao, Ben-Yang; Chen, Pei-Chen; Kao, Hsien‐Li; Kuo, Han-Chun; Kuo, Ching‐Hua; Chiu, Tina H.T.; Chen, Rou-An; Chuang, Hsiao-Li; Huang, Yen-Te; Zou, Hsin-Bai; Hsu, Cheng-Chih; Chang, Ting-Yan; Lin, Chin-Lon; Ho, Chi‐Tang; Yu, Hon‐Tsen; Sheen, Lee‐Yan; Wu, Ming–Shiang

doi:10.1136/gutjnl-2018-317155

Cited by 134 publications

(157 citation statements)

References 38 publications

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“…In individuals with normal renal function, the efficient urinary excretion of TMAO keeps a low level of average blood TMAO. The concentration of blood TMAO can also be affected by foods consumed within the preceding 24 hours . In fact, fluctuations of blood TMAO occur due to varied material inputs and rapid urinary excretion.…”

Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

“…Therefore, we presumed that a spot measurement of blood TMAO may not be sufficiently representative for the TMAO‐producing function of the gut microbiota in the human body. Thus, we proposed an oral carnitine challenge test to measure the TMAO production capacity of the gut microbiota as a whole …”

Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

“…After providing experimental participants with a specific quantity of fermentable food components, the targeted microbial metabolome can be measured in clinical samples – including blood, urine, and stool – at indicated times. We first proposed the oral carnitine challenge test as a functional test to measure the TMAO production capacity of gut microbiota provided with sufficient non‐isotope‐labeled carnitine for in vivo microbial fermentation (Figure B). To establish a challenge test for the measurement of gut microbial fermentation capacity, a pharmacokinetic study is required to define the amount of input raw materials and subsequent sampling time points for analysis .…”

Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

“…We first proposed the oral carnitine challenge test as a functional test to measure the TMAO production capacity of gut microbiota provided with sufficient non‐isotope‐labeled carnitine for in vivo microbial fermentation (Figure B). To establish a challenge test for the measurement of gut microbial fermentation capacity, a pharmacokinetic study is required to define the amount of input raw materials and subsequent sampling time points for analysis . Blood, urine, and fecal samples can be selected on the basis of the absorption rate, host biotransformation, and excretory pathways of the targeted microbial metabolites.…”

Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

“…Studies have suggested that gut microbiota‐derived metabolites play key roles in health maintenance and disease progression . They may also serve as novel biomarkers in clinical diagnosis and prognosis . In this article, we discuss and highlight some of the most important literature about the mass spectrometry‐based analysis of gut microbial metabolites and their relationships to translational research for future clinical applications.…”

Section: Introductionmentioning

confidence: 99%

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Measurement of gut microbial metabolites in cardiometabolic health and translational research

Hsu

Sheen

et al. 2020

Rapid Comm Mass Spectrometry

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The human gut microbiota is a functioning endocrine organ and stands at the intersection between dietary components and health or disease. There are very many microbial metabolites with numerous structures and functions arising from the gut microbial fermentation of foods and become signals for biological communication in the human body. These small molecules can be absorbed and delivered to distant organs through the circulatory system to build the gut–systemic axis. The gut microbial metabolomes are thus believed to play important roles in regulating cardiometabolic health and provide opportunities in mechanistic research and new drug discovery. Measurement of these novel microbial metabolites in clinical samples may serve as a tool for investigating disease biomarkers. In the past decade, the development of untargeted and targeted metabolomics approaches using NMR, LC/MS, and GC/MS has contributed to the exploration of gut microbial metabolomes in cardiometabolic health and disease. Some important targets are currently being translated into clinical applications. In this review article, we introduce an oral carnitine challenge test developed as an example to demonstrate the potential applications in personalized nutrition based on the function of gut microbiota. It is a method taking the gut microbiota as a bioreactor and provides fermentable materials as inputs and measures the outputs of targeted microbial byproducts in the blood or urine. This challenge test may be extended to measure metabolites from microbial fermentation related to other endocrinological or inflammatory diseases. We review current gut metabolome research approaches and propose a gut microbial functional measurement using a challenge test. We suggest that the maturation in measuring gut microbial metabolites may provide an important piece to complete the puzzle of precision medicine.

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Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

Section: Functional Measurement Of Gut Microbiota Using An Oral Challmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Measurement of gut microbial metabolites in cardiometabolic health and translational research

Hsu

Sheen

et al. 2020

Rapid Comm Mass Spectrometry

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Human Gut Microbiota in Cardiovascular Disease

Ronen,

Rokach,

Abedat

et al. 2024

Comprehensive Physiology

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The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N ‐oxide (TMAO), short‐chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449‐5490, 2024.

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Ethnic differences in association of outcomes with trimethylamine N‐oxide in acute heart failure patients

et al. 2020

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Aims The aim of this study was to investigate whether ethnicity influences the associations between trimethylamine N-oxide (TMAO) levels and heart failure (HF) outcomes. Methods and results Trimethylamine N-oxide levels were measured in two cohorts with acute HF at two sites. The UK Leicester cohort consisted mainly of Caucasian (n = 842, 77%) and South Asian (n = 129, 12%) patients, whereas patients in the Japanese cohort (n = 116, 11%) were all Japanese. The primary endpoint was the measurement of all-cause mortality and/or HF rehospitalization within 1 year post-admission. Association of TMAO levels with outcome was compared in the entire population and between ethnic groups after adjustment for clinical parameters. TMAO levels were significantly higher in Japanese patients [median (interquartile range): 9.9 μM (5.2-22.8)] than in Caucasian [5.9 μM (3.6-10.8)] and South Asian [4.5 μM (3.1-8.4)] (P < 0.001) patients. There were no differences in the rate of mortality and/or HF rehospitalization between the ethnic groups (P = 0.096). Overall, higher TMAO levels showed associations with mortality and/or rehospitalization after adjustment for confounders (P = 0.002). Despite no differences between ethnicity and association with mortality/HF after adjustment (P = 0.311), only in Caucasian patients were TMAO levels able to stratify for a mortality/HF event (P < 0.001). Conclusions Differences were observed in the association of mortality and/or rehospitalization based on circulating TMAO levels. Elevated TMAO levels in Caucasian patients showed increased association with adverse outcomes, but not in non-Caucasian patients.

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Identification of TMAO-producer phenotype and host–diet–gut dysbiosis by carnitine challenge test in human and germ-free mice

Cited by 134 publications

References 38 publications

Measurement of gut microbial metabolites in cardiometabolic health and translational research

Measurement of gut microbial metabolites in cardiometabolic health and translational research

Human Gut Microbiota in Cardiovascular Disease

Ethnic differences in association of outcomes with trimethylamine N‐oxide in acute heart failure patients

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