Trimethylamine-N-oxide (TMAO) as Novel Potential Biomarker of Early Predictors of Metabolic Syndrome

Abstract

There is a mechanistic link between the gut-derived metabolite trimethylamine-N-oxide (TMAO) and obesity-related diseases, suggesting that the TMAO pathway may also be linked to the pathogenesis of obesity. The Visceral Adiposity Index (VAI), a gender-specific indicator of adipose dysfunction, and the Fatty Liver Index (FLI), a predictor of non-alcoholic fatty liver disease (NAFLD), are early predictors of metabolic syndrome (MetS). In this cross-sectional observational study, we investigated TMAO levels in adults stratified according to Body Mass Index (BMI) and the association of TMAO with VAI and FLI. One hundred and thirty-seven adult subjects (59 males; 21–56 years) were enrolled. TMAO levels were detected using HPLC/MS analysis. Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), VAI and FLI were included as cardio-metabolic indices. TMAO levels increased along with BMI and were positively associated with VAI and FLI, independently, on common potential covariates. The most sensitive and specific cut-offs for circulating levels of TMAO to predict the presence of NAFLD-FLI and MetS were ≥8.02 µM and ≥8.74 µM, respectively. These findings allow us to hypothesize a role of TMAO as an early biomarker of adipose dysfunction and NAFLD-FLI in all borderline conditions in which overt MetS is not present, and suggest that a specific cut-off of TMAO might help in identifying subjects at high risk of NAFLD.

Gut microbiota‐derived metabolite trimethylamine N‐oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose‐response meta‐ analysis

“…Increased TMAO concentration in the current meta‐analysis was associated with increased BMI both in the two‐class meta‐analysis and the dose‐response synthesis. The positive association between obesity and TMAO was shown in several previous studies . In conclusion, in the current meta‐analysis, for the first time, the results of studies investigating the association between circulating TMAO and BMI in a dose‐dependent and two‐class meta‐analysis were summarized.…”

“…After that dose, the curve is rather slope. Similarly, Barrea et al suggested cut offs of greater than or equal to 8.02 μM and greater than or equal to 8.74 μM for circulating TMAO in prediction of non‐alcoholic fatty liver disease and metabolic syndrome, respectively. In the current meta‐analysis, a positive association between circulating TMAO and BMI in a dose‐dependent manner was confirmed in studies involved apparently healthy individuals ( P nonlinearity = .007).…”

“…Egg yolks, milk, dairy products, organ and muscle meats, and seafood such as mollusks, crustaceans, and fish are major dietary sources of TMAO and its precursors, although whether circulating TMAO is affected by dietary source needs to be further evaluated . There are numerous studies regarding the association between TMAO and biomarkers or risk factors of CVD, increased insulin resistance, impaired glucose metabolism, and metabolic syndrome . Possible suggested mechanisms about the association between TMAO and cardiovascular risk factors could be increased cholesterol accumulation in macrophages and in foam cells of artery walls or increased human platelet hyper‐responsiveness and potential of thrombosis in higher TMAO concentrations.…”

“…TMAO substrate metabolites are abundant in foods rich in carnitine, choline, and lecithin, including egg yolks, milk, dairy products, organ and muscle meats, and seafood such as mollusks, crustaceans, and fish . Recently, several studies have found a possible role for TMAO in chronic disease including CVD and mortality diabetes, chronic kidney disease and metabolic syndrome . In a cross‐sectional study among 1286 Canadians, the highest quintile of serum TMAO was associated with increased prevalent CVD after adjustment for potential confounders (OR, 9.33; CI, 1.88‐46.37; P = .006).…”

Gut microbial-related metabolite trimethylamine-N-oxide and its precursor L-carnitine are associated with spontaneous preterm birth: a nested case-control study

“…Therefore, low TMAO and carnitine status of pregnant women may lead to malnutrition, organ dysfunction, and embryonic development restriction. In addition, TMAO synthesized by the intestinal microbiota has been demonstrated as early predictors of metabolic syndrome, and strong linked with atherosclerosis, type 2 diabetes, vitamin D deficiency and chronic kidney disease [10][11][12]34]. The metabolic syndrome induced by TMAO caused increased sPTB risk [13,14].…”