Gut microbiota alterations may be related to insulin resistance, diabetes, and the impaired amino acid metabolism. We investigated whether changes in gut microbiota metabolite of trimethylamine N-oxide (TMAO) and its precursors (choline and L-carnitine) were associated with improvements of diabetes-related traits and diabetes-risk-related amino acids in a weight-loss diet intervention. This study included 504 obese adults who were randomly assigned to 1 of 4 energy-reduced diets varying in the macronutrient composition. We calculated changes (Δ) in TMAO, choline, and L-carnitine from baseline to 6 months after the diet intervention. Greater decreases in choline and L-carnitine were significantly (p <0.05) associated with greater improvements in fasting insulin levels and the Homeostatic Model Assessment of Insulin Resistance of insulin resistance (HOMA-IR) at 6 months. Particularly, the reduction of choline was predictive of long-term (2-year) improvements in fasting glucose (p=0.007), insulin (p=0.002), and HOMA-IR (p <0.001). We found significant interactions between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin, and HOMA-IR (Pinteraction <0.05); among participants who consumed a high-fat diet, greater increase in TMAO was related to less improvements of the outcomes. In addition, ΔL-carnitine and Δcholine were also significantly related to changes in amino acids (including branched-chain and aromatic amino acids). However, the associations of ΔTMAO, Δcholine, and ΔL-carnitine with the diabetes-related traits were independent of the changes in amino acids.

In conclusion, weight-loss-diet-induced changes in TMAO, choline, and L-carnitine were significantly associated with the improvements in glycemia and insulin sensitivity, regardless concurrent changes in diabetes-risk related amino acids. Dietary fat intake may modify the associations of changes in TMAO with the improvements of diabetes-related traits.


Y. Heianza: None. D. Sun: None. G. Bray: Advisory Panel; Self; Herbalife International of America, Inc., Novo Nordisk A/S. L. Qi: None.

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