We investigated the hypothesis that the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system with important functions in the CNS, may play a role in the microbiota-gut-brain axis. Using LC-MS/MS and qPCR arrays we profiled the brain eCBome of juvenile (4 weeks) and adult (13 weeks) male and female germ-free (GF) mice, which are raised in sterile conditions and virtually devoid of microbiota, present neurophysiological deficits, and were found recently to exhibit a strongly altered gut eCBome in comparison to conventionally raised age/sex-matched controls. The causal effect of the gut microbiome on the eCBome was investigated through the re-introduction into adult male GF mice of a functional gut microbiota by fecal microbiota transfer (FMT). The concentrations of the eCB, 2-arachidonoylglycerol (2-AG), and its 2-monoacylglycerol congeners, were significantly reduced in the brain, but not in the hypothalamus, of both juvenile and adult male and adult female GF mice. FMT rendered these decreases non-statistically significant. The eCB, anandamide (AEA), and its congener N-acylethanolamines (NAEs), were instead increased in the brain of adult female GF mice. Saturated fatty acid-containing NAEs were decreased in adult male GF mouse hypothalamus in a manner not reversed by FMT. Only few changes were observed in the expression of eCBome enzymes and receptors. Our data open the possibility that altered eCBome signaling may underlie some of the brain dysfunctions typical of GF mice.

我们调查了这一假设，即内源性大麻素（eCBome）是内源性大麻素（eCB）信号系统在中枢神经系统中具有重要功能的延伸，可能在微生物群-肠脑轴中起作用。我们使用LC-MS / MS和qPCR阵列对未成年（4周）和成年（13周）雄性和雌性无菌（GF）小鼠的大脑eCBome进行了分析，这些小鼠在无菌条件下饲养并且几乎没有微生物神经生理缺陷，最近发现与传统的年龄/性别匹配对照组相比，肠道eCBome发生了强烈变化。通过粪便微生物群转移（FMT）将功能性肠道菌群重新引入成年雄性GF小鼠中，研究了肠道微生物群对eCBome的因果关系。eCB，2-花生四烯酰甘油（2-AG），幼年和成年雄性和成年雌性GF小鼠的脑部，但在下丘脑中均没有明显降低其2-单酰基甘油的同源物。FMT使得这些下降没有统计学意义。eCB，anandamide（AEA）及其同类物相反，成年雌性GF小鼠的大脑中N-酰基乙醇胺（NAE）增加。成年雄性GF小鼠下丘脑中饱和脂肪酸的NAE含量降低，而FMT不能逆转。eCBome酶和受体的表达仅观察到很少的变化。我们的数据揭示了改变的eCBome信号可能是GF小鼠典型的某些脑功能障碍的可能性。