Alterations and correlations of gut microbiota, fecal, and serum metabolome characteristics in a rat model of alcohol use disorder

Xiaolong Wang; Lin Li; Cong Bian; Mingjian Bai; Haitao Yu; Han Gao; Jiaxin Zhao; Chunjing Zhang; Rongjie Zhao

doi:10.3389/fmicb.2022.1068825

Alterations and correlations of gut microbiota, fecal, and serum metabolome characteristics in a rat model of alcohol use disorder

Front Microbiol. 2023 Jan 4:13:1068825. doi: 10.3389/fmicb.2022.1068825. eCollection 2022.

Authors

Xiaolong Wang¹, Lin Li¹, Cong Bian¹, Mingjian Bai¹, Haitao Yu¹, Han Gao¹, Jiaxin Zhao², Chunjing Zhang¹, Rongjie Zhao³

Affiliations

¹ Department of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
² National and Local United Engineering Laboratory for Chinese Herbal Medicine Breeding and Cultivation, School of Life Sciences, Jilin University, Changchun, China.
³ Department of Psychiatry, Qiqihar Medical University, Qiqihar, Heilongjiang, China.

Abstract

Background: 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.

Methods: 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.

Results: 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 Romboutsia and Turicibacter were significantly increased, whereas uncultured_bacterium_o_Mollicutes_RF39 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.

Conclusion: 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.

Keywords: alcohol preference; alcohol use disorder; fecal metabolites; gut microbiota; serum metabolites.