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Sci Rep. 2016 Jan 8;6:19076. doi: 10.1038/srep19076.

Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults.

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School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
Faculty of Public Health, School of Medicine, Jinan University, Guangzhou (510632), People's Republic of China.
Research and Therapy Center for Liver Disease, the Affiliated Dongnan Hospital of Xiamen University, Zhangzhou (363000), People's Republic of China.
Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, University of Sun Yat-Sen, Guangzhou (510120), People's Republic of China.


Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18-60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants.

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