Objective Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention.
Design We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated.
Results Greater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (pinteraction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids.
Conclusion Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism.
Trial registration number NCT00072995.
- glucose metabolism
- clinical trials
- amino acids
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Contributors YH contributed to the study concept and design, analysis and interpretation of data, drafting and revising the manuscript, statistical analysis and study supervision. DS and XL contributed analysis and interpretation of data, and drafting and revising the manuscript. JAD contributed measurements and interpretation of data, and drafting and revising the manuscript. GAB and FMS contributed to acquisition of data, interpretation of data and drafting and revising the manuscript. LQ contributed to the study concept and design, acquisition of data, analysis and interpretation of data, drafting and revising the manuscript, statistical analysis and funding and study supervision. LQ had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding The study is supported by National Institutes of Health (NIH) grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200) and USA–Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N). YH is a recipient of a Grant-in-Aid for Scientific Research and Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science.
Competing interests None declared.
Patient consent Not required.
Ethics approval The trial was conducted at two sites, one in Boston at the Harvard School of Public Health and Brigham & Women’s Hospital and the other in Baton Rouge at the Pennington Biomedical Research Center of the Louisiana State University System.The study was approved by the human subjects committee at each institution and by data and safety monitoring board appointed by the National Heart, Lung and Blood Institute. All participants gave written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.