Castonguay-Paradis Sophie, Parent Lydiane, St-Arnaud Gabrielle, Perron Julie, Dumais Élizabeth, Flamand Nicolas, Raymond Frédéric, Di Marzo Vincenzo, Veilleux Alain
Centre Nutrition, Santé et Société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC, Canada, G1V 0A6.
École de nutrition, Faculté des sciences de l'agriculture et de l'alimentation (FSAA), Université Laval, Québec, QC, Canada, G1V 0A6.
J Clin Endocrinol Metab. 2025 Feb 18;110(3):739-747. doi: 10.1210/clinem/dgae586.
The endocannabinoid system and its extension, the endocannabinoidome (eCBome), are involved in numerous biological processes, notably energy homeostasis, across virtually all tissues. While the circulating eCBome mediator profile is associated with dietary intakes and metabolic status, an important knowledge gap resides in the identification of the precise determinants of these mediators in the gut lumen.
We aimed at establishing the profile of eCBome mediators in human feces and investigating their association with circulating eCBome mediators, dietary intakes, metabolic status, and gut microbiota composition.
N-acyl-ethanolamines (NAEs) and 2-monoacyl-glycerols (2-MAGs) were profiled by liquid chromatography coupled to tandem mass spectrometry in plasma and feces of a cross-sectional cohort (n = 195) and a short-term dietary intervention trial (n = 21) with comprehensive dietary intakes and gut microbiota measures.
Six NAEs and 7 2-MAGs were identified in fecal samples, but some, especially omega-3-derived mediators, were undetectable in the majority of samples. Fecal NAEs, and to a lower extent 2-MAGs, were positively albeit weakly correlated with the circulating levels of eCBome mediators. Fecal 2-arachidonoyl-glycerol, N-palmitoyl-ethanolamine, and N-docosahexaenoyl-ethanolamine levels were positively associated with visceral adiposity and with some parameters of the metabolic profile. Dietary intakes of foods rich in fibers were associated with lower fecal levels of several eCBome mediators, while intakes of unsaturated fatty acids were associated with fecal 2-oleoyl-glycerol and 2-linoleoyl-glycerol. Interestingly, gut microbiota diversity and composition were a strong correlate of the fecal eCBome profile.
The fecal eCBome profile is associated with gut microbiota composition and dietary intakes, more than with the circulating profile. These results strengthen the hypothesis of an interrelation between the gut microbiome and eCBome signaling involved in the regulation of numerous host biological processes.
内源性大麻素系统及其扩展——内源性大麻素组（eCBome），参与了几乎所有组织中的众多生物过程，尤其是能量稳态。虽然循环中的eCBome介质谱与饮食摄入和代谢状态相关，但在确定肠道腔内这些介质的确切决定因素方面存在重要的知识空白。
我们旨在确定人类粪便中eCBome介质的谱，并研究它们与循环中的eCBome介质、饮食摄入、代谢状态和肠道微生物群组成的关联。
采用液相色谱-串联质谱法对一个横断面队列（n = 195）和一项短期饮食干预试验（n = 21）的血浆和粪便中的N-酰基乙醇胺（NAEs）和2-单酰甘油（2-MAGs）进行分析，同时对饮食摄入和肠道微生物群进行全面测量。
在粪便样本中鉴定出6种NAEs和7种2-MAGs，但其中一些，尤其是ω-3衍生的介质，在大多数样本中无法检测到。粪便中的NAEs，以及程度较低的2-MAGs，与eCBome介质的循环水平呈正相关，尽管相关性较弱。粪便中2-花生四烯酰甘油、N-棕榈酰乙醇胺和N-二十二碳六烯酰乙醇胺水平与内脏肥胖和一些代谢谱参数呈正相关。富含纤维食物的饮食摄入与几种eCBome介质的粪便水平较低有关，而不饱和脂肪酸的摄入与粪便中的2-油酰甘油和2-亚油酰甘油有关。有趣的是，肠道微生物群的多样性和组成与粪便eCBome谱密切相关。
粪便eCBome谱与肠道微生物群组成和饮食摄入的关联，大于与循环谱的关联。这些结果强化了肠道微生物群与参与众多宿主生物过程调节的eCBome信号之间存在相互关系的假设。
