RT Journal Article
SR Electronic
T1 Identification of TMAO-producer phenotype and host–diet–gut dysbiosis by carnitine challenge test in human and germ-free mice
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1439
OP 1449
DO 10.1136/gutjnl-2018-317155
VO 68
IS 8
A1 Wei-Kai Wu
A1 Chieh-Chang Chen
A1 Po-Yu Liu
A1 Suraphan Panyod
A1 Ben-Yang Liao
A1 Pei-Chen Chen
A1 Hsien-Li Kao
A1 Han-Chun Kuo
A1 Ching-Hua Kuo
A1 Tina H T Chiu
A1 Rou-An Chen
A1 Hsiao-Li Chuang
A1 Yen-Te Huang
A1 Hsin-Bai Zou
A1 Cheng-Chih Hsu
A1 Ting-Yan Chang
A1 Chin-Lon Lin
A1 Chi-Tang Ho
A1 Hon-Tsen Yu
A1 Lee-Yan Sheen
A1 Ming-Shiang Wu
YR 2019
UL http://gut.bmj.com/content/68/8/1439.abstract
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.