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

• Published in: Scientific reports Vol. 6; no. 1; p. 19076
• Main Authors: Chen, Yu-ming, Liu, Yan, Zhou, Rui-fen, Chen, Xiao-ling, Wang, Cheng, Tan, Xu-ying, Wang, Li-jun, Zheng, Rui-dan, Zhang, Hong-wei, Ling, Wen-hua, Zhu, Hui-lian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.01.2016; Nature Publishing Group
• Subjects: 692/308/174; 692/499; 692/699/1503/1607/2750; Adolescent; Adult; Aged; Betaine; Betaine - blood; Biomarkers - blood; Biopsy; Cardiovascular diseases; Case-Control Studies; Choline; Choline - biosynthesis; Choline - blood; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Fatty liver; Female; Gastrointestinal Microbiome; Health risk assessment; High-performance liquid chromatography; Humanities and Social Sciences; Humans; Intestinal microflora; Liver diseases; Male; Methylamines - blood; Middle Aged; multidisciplinary; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - diagnostic imaging; Non-alcoholic Fatty Liver Disease - pathology; Science; Serum levels; Severity of Illness Index; Steatosis; Tandem Mass Spectrometry; Trimethylamine; Trimethylamine-N-oxide; Ultrasonography
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep19076

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.