Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial. Issue 2 (2nd June 2018)

• Record Type: Journal Article
• Authors: Heianza, Yoriko; Sun, Dianjianyi; Li, Xiang; DiDonato, Joseph A; Bray, George A; Sacks, Frank M; Qi, Lu
• Is Part Of: Gut. Volume 68:Issue 2(2019)
• Page Start: 263
• Page End: 270
• Publication Date: 2018-06-02
• Subjects: glucose metabolism -- clinical trials -- amino acids -- nutrition; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2018-316155
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : 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 .