Prebiotic inulin alleviates anxiety and depression-like behavior in alcohol withdrawal mice by modulating the gut microbiota and 5-HT metabolism.

Autor: Li K; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Wei W; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Xu C; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Lian X; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Bao J; Department of Geriatric Psychiatry, The Mental Hospital of Yunnan Province, Kunming, 650224, China., Yang S; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Wang S; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Zhang X; Department of Psychiatry/Alcohol Dependence Treatment, The Mental Hospital of Yunnan Province, Kunming, 650224, China., Zheng X; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Wang Y; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China., Zhong S; School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China; NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, 650500, China; Forensic Biology Identification Laboratory, Judicial Identification Center of Kunming Medical University, Kunming, 650500, China. Electronic address: zhongshurong@hotmail.com.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Dec; Vol. 135, pp. 156181. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1016/j.phymed.2024.156181
Abstrakt: Background: Alcohol dependence (AD) is a common psychiatric disorder, often accompanied by anxiety and depression. These comorbidities are linked to disturbances in serotonin (5-HT) metabolism and gut microbiota dysbiosis. Clinical studies suggest that inulin, a prebiotic, can alleviate anxiety and depression in AD patients by affecting the gut microbiota, although the mechanisms remain unclear.
Purpose: The purpose of this study is to investigate the potential mechanisms by which inulin, a prebiotic, improves anxiety and depression-like behaviors in AD withdrawal mice. This research is based on the drug and food homology and intestinal treatment of encephalopathy, with the goal of developing new clinical strategies for AD treatment.
Study Design: For this purpose, fecal samples from AD patients were analyzed to identify microorganisms associated with AD. An AD withdrawal mouse model was created, with inulin as the intervention and fluvoxamine maleate as the control. Techniques such as 16S microbiome sequencing and UPLC-TQMS-targeted metabolomics were used to assess gut microbiota, short-chain fatty acids (SCFAs) levels, and 5-HT metabolism.
Methods: The AD withdrawal model was built using the "Drinking-in-the-dark" protocol over 6 weeks. Inulin (2 g/kg/day) and fluvoxamine maleate (30 mg/kg/day) were administered for 4 weeks. The open field test, forced swim test, and tail suspension test were used to evaluate anxiety and depression-like behaviors in mice. ELISA and qRT-PCR assessed 5-HT metabolism in the colon, blood, and prefrontal cortex, while 16S microbiome sequencing analyzed changes in gut microbiota and UPLC-TQMS examined SCFAs levels. Immunohistochemistry was used to study intestinal barrier integrity.
Results: AD patients showed reduced SCFA-producing bacteria such as Faecalibacterium and Roseburia. In mice, AD withdrawal led to anxiety and depression-like behaviors, disrupted 5-HT metabolism, and gut microbiota dysbiosis. Inulin supplementation alleviated these behaviors, increased 5-HT and 5-hydroxytryptophan (5-HTP) levels, upregulated colonic tryptophan hydroxylase 1 (TPH1) expression, and promoted the growth of beneficial bacteria such as Faecalibacterium and Roseburia, while also increasing SCFAs levels.
Conclusion: Inulin increases the abundance of Faecalibacterium and Roseburia, enhances SCFAs production, and regulates 5-HT metabolism, improving anxiety and depression-like behaviors in AD withdrawal mice. These findings suggest that inulin may serve as a nutritional intervention for mental health in AD patients by targeting the microbiome-gut-brain axis.
Competing Interests: Declaration of competing interest All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy. The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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