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.

Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes

“…In addition, a relevant interaction was found between plasma TMAO and alcoholic beverage drinking status in this study, with a stronger association observed in participants who drank alcoholic beverages. The effect modification may be due in part to the effect of alcohol intake on liver function, given that TMAO has been associated with fatty liver disease (11). Further studies are warranted to validate this interaction and explore potential mechanisms.…”

The role of trimethylamine N-oxide as a mediator of cardiovascular complications in chronic kidney disease

“…Subpopulations of gut microbiota vary widely between individuals and can have a measureable impact upon whole body nutrition, metabolism and immune function. 8 Potentially toxic metabolites may arise from alterations in gut microbiota in a range of disorders such as obesity, 9 impaired glucose tolerance 10 and liver disease, 11 suggesting that the usual symbiotic relationship between gut microbiota and host may turn dysbiotic in these conditions, allowing gut flora to exacerbate disease. In addition, the gut microbiome has been implicated as a source of pathogenic mediators in the context of CKD.…”

Trimethylamine‐N‐oxide promotes brain aging and cognitive impairment in mice

“…Recently, trimethylamine‐ N ‐oxide (TMAO), a product of choline, which is metabolized by the gut flora, has attracted increasing interest in medical research. TMAO is involved in a variety of diseases, including cardiovascular events (Tang et al., 2013), atherosclerosis (Koeth et al., 2013), obesity, diabetes (Gao et al., 2014), chronic kidney disease (Missailidis et al., 2016), nonalcoholic liver disease (Chen et al., 2016), Alzheimer's disease (Xu & Wang, 2016), peripheral arterial disease (Senthong et al., 2016), and tumours (Guertin et al., 2017). However, the influence of TMAO in the aging process, including brain aging, has not yet been reported.…”