title: Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults.
abstract: 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.
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Rui-fen
authors.initials: RF
authors.lastname: Zhou
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Chen
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Xu-ying
authors.initials: XY
authors.lastname: Tan
authors.affiliation: Faculty of Public Health, School of Medicine, Jinan University, Guangzhou (510632), People's Republic of China.
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Research and Therapy Center for Liver Disease, the Affiliated Dongnan Hospital of Xiamen University, Zhangzhou (363000), People's Republic of China.
authors.forename: Rui-dan
authors.initials: RD
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, University of Sun Yat-Sen, Guangzhou (510120), People's Republic of China.
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Ling
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou (510080), People's Republic of China.
authors.forename: Hui-lian
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001622:Betaine / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002794:Choline / Q000096:biosynthesis / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology*; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D008744:Methylamines; D001622:Betaine; C005855:trimethyloxamine; D002794:Choline