PT  - JOURNAL ARTICLE
AU  - Wei-Kai Wu
AU  - Chieh-Chang Chen
AU  - Po-Yu Liu
AU  - Suraphan Panyod
AU  - Ben-Yang Liao
AU  - Pei-Chen Chen
AU  - Hsien-Li Kao
AU  - Han-Chun Kuo
AU  - Ching-Hua Kuo
AU  - Tina H T Chiu
AU  - Rou-An Chen
AU  - Hsiao-Li Chuang
AU  - Yen-Te Huang
AU  - Hsin-Bai Zou
AU  - Cheng-Chih Hsu
AU  - Ting-Yan Chang
AU  - Chin-Lon Lin
AU  - Chi-Tang Ho
AU  - Hon-Tsen Yu
AU  - Lee-Yan Sheen
AU  - Ming-Shiang Wu
TI  - Identification of TMAO-producer phenotype and host–diet–gut dysbiosis by carnitine challenge test in human and germ-free mice
AID  - 10.1136/gutjnl-2018-317155
DP  - 2019 Aug 01
TA  - Gut
PG  - 1439--1449
VI  - 68
IP  - 8
4099  - http://gut.bmj.com/content/68/8/1439.short
4100  - http://gut.bmj.com/content/68/8/1439.full
SO  - Gut2019 Aug 01; 68
AB  - Objective The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.Design A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.Results The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.Conclusion The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.Trial registration number NCT02838732; Results.