Wang Xiaolong, Li Lin, Bian Cong, Bai Mingjian, Yu Haitao, Gao Han, Zhao Jiaxin, Zhang Chunjing, Zhao Rongjie
Department of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
National and Local United Engineering Laboratory for Chinese Herbal Medicine Breeding and Cultivation, School of Life Sciences, Jilin University, Changchun, China.
Front Microbiol. 2023 Jan 4;13:1068825. doi: 10.3389/fmicb.2022.1068825. eCollection 2022.
Growing evidence suggests the gut microbiota and metabolites in serum or fecal may play a key role in the process of alcohol use disorder (AUD). However, the correlations of gut microbiota and metabolites in both feces and serum in AUD subjects are not well understood.
We established a rat model of AUD by a chronic intermittent ethanol voluntary drinking procedure, then the AUD syndromes, the gut microbiota, metabolomic profiling in feces and serum of the rats were examined, and correlations between gut microbiota and metabolites were analyzed.
Ethanol intake preference increased and maintained at a high level in experimental rats. Anxiety-like behaviors was observed by open field test and elevated plus maze test after ethanol withdraw, indicating that the AUD rat model was successfully developed. The full length 16S rRNA gene sequencing showed AUD significantly changed the β-diversity of gut microbial communities, and significantly decreased the microbial diversity but did not distinctly impact the microbial richness. Microbiota composition significantly changed in AUD rats, such as the abundance of and were significantly increased, whereas was decreased. In addition, the untargeted metabolome analysis revealed that many metabolites in both feces and serum were altered in the AUD rats, especially involved in sphingolipid metabolism and glycerophospholipid metabolism pathways. Finally, multiple correlations among AUD behavior, gut microbiota and co-changed metabolites were identified, and the metabolites were directly correlated with the gut microbiota and alcohol preference.
The altered metabolites in feces and serum are important links between the gut microbiota dysbiosis and alcohol preference in AUD rats, and the altered gut microbiota and metabolites can be potentially new targets for treating AUD.
越来越多的证据表明，肠道微生物群以及血清或粪便中的代谢产物可能在酒精使用障碍（AUD）的过程中起关键作用。然而，AUD患者粪便和血清中肠道微生物群与代谢产物之间的相关性尚未完全明确。
我们通过慢性间歇性乙醇自愿饮用程序建立了AUD大鼠模型，然后检测大鼠的AUD综合征、肠道微生物群、粪便和血清中的代谢组学谱，并分析肠道微生物群与代谢产物之间的相关性。
实验大鼠的乙醇摄入量偏好增加并维持在较高水平。乙醇戒断后通过旷场试验和高架十字迷宫试验观察到类似焦虑的行为，表明成功建立了AUD大鼠模型。全长16S rRNA基因测序显示，AUD显著改变了肠道微生物群落的β多样性，显著降低了微生物多样性，但对微生物丰富度没有明显影响。AUD大鼠的微生物群组成发生了显著变化，例如[具体菌属1]和[具体菌属2]的丰度显著增加，而[具体菌属3]减少。此外，非靶向代谢组分析显示，AUD大鼠粪便和血清中的许多代谢产物都发生了改变，尤其是涉及鞘脂代谢和甘油磷脂代谢途径。最后，确定了AUD行为、肠道微生物群和共同变化的代谢产物之间的多种相关性，这些代谢产物与肠道微生物群和酒精偏好直接相关。
粪便和血清中代谢产物的改变是AUD大鼠肠道微生物群失调与酒精偏好之间的重要联系，肠道微生物群和代谢产物的改变可能是治疗AUD的潜在新靶点。
