Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial.

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial.
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DOI:
10.1136/gutjnl-2018-316155
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发表时间:
2019-03
期刊:
Gut
影响因子:
24.5
通讯作者:
Qi L
Qi L
中科院分区:
医学1区
文献类型:
--
作者:
Heianza Y;Sun D;Li X;DiDonato JA;Bray GA;Sacks FM;Qi L

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肠道微生物群的改变与宿主胰岛素抵抗、糖尿病和氨基酸代谢受损有关。我们研究了在减肥饮食干预中,肠道微生物群依赖的三甲胺N-氧化物(TMAO)代谢物及其营养前体(胆碱和L-肉碱)的变化是否与葡萄糖代谢和糖尿病相关氨基酸的改善相关。我们纳入了504名超重和肥胖的成年人,他们被随机分配到4种能量减少饮食中的1种,这些饮食在大量营养素摄入方面各不相同。计算干预后TMAO、胆碱和L-肉碱水平的6个月变化(Δ)。胆碱和L-肉碱的更大降低与6个月时空腹胰岛素浓度和胰岛素抵抗稳态模型评估(HOMA-IR)的更大改善显著相关(p <0.05)。胆碱的减少与葡萄糖和胰岛素抵抗的2年改善显著相关。我们发现膳食脂肪摄入量与ΔTMAO对空腹血糖、胰岛素和HOMA-IR的影响存在显著联系(P交互作用<0.05);在高脂肪饮食的参与者中,TMAO的增加与结局改善程度的降低有关。此外,Δ L-肉毒碱和Δ胆碱与氨基酸(包括支链氨基酸和芳香族氨基酸)的变化显著相关。有趣的是,ΔTMAO、Δ胆碱和Δ L-肉碱与糖尿病相关性状的关联与氨基酸的变化无关。我们的研究结果强调了TMAO,胆碱和L-肉毒碱的变化在肥胖患者减肥干预期间改善胰岛素敏感性的重要性。膳食脂肪摄入可能会改变TMAO与胰岛素敏感性和葡萄糖代谢的关系。
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. We included 504 overweight and obese adults who were randomly assigned to 1 of 4 energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline, and L-carnitine levels after the intervention were calculated. 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. 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.
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