Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

中文翻译：

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Akkermansia muciniphila的有益作用与循环内源性大麻素组的重大变化无关，但与新的PPARα激动剂相关的单棕榈酰甘油甘油水平较高有关

在肥胖症和相关的代谢紊乱的背景下，粘蛋白阿克曼（Akkermansia muciniphila）被认为是下一代有益细菌之一。尽管已经在人类代谢综合症的背景下确立了其有益作用的第一个概念证明，但其机理尚不完全清楚。这项研究旨在破译细菌是否通过调节内源性大麻素组（eCBome）发挥其有益的特性。在进行3个月的干预（包括每天摄入活的或巴氏杀菌的）之后，通过超重或肥胖个体血浆中的串联质谱（LC-MS / MS）定量测定25种内源性内源性大麻素相关脂质的循环水平粘菌。多元分析的结果表明，黏液曲霉的有益作用与eCBome的整体修饰无关。但是，随后的单变量分析表明，在安慰剂组中观察到的两种棕榈油脂质中的1个棕榈酰甘油（1-PG）和2个棕榈酰甘油（2-PG）的减少被活细菌显着抵消，并且通过巴氏灭菌形式在较低程度上。我们还发现1-和2-PG是过氧化物酶体增殖物激活受体α（PPARα）的内源性激活剂。我们假设单棕榈酰甘油对PPARα的激活可能是人粘液曲霉在人类代谢综合征中诱导的有益代谢作用的一部分。