114027
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
氟西汀和丁酸对慢性不可预测轻度应激所致便秘的缓解作用及其对肠道微生态的影响
Authors Li X, Suo J, Yao S, Tian B, Zhao Z, Wang Y, Li X, Jin D, Yang X
Received 30 July 2025
Accepted for publication 10 December 2025
Published 26 December 2025 Volume 2025:19 Pages 11675—11695
DOI https://doi.org/10.2147/DDDT.S552593
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Anastasios Lymperopoulos
Xuzhao Li,1,* Jing Suo,2,* Shiqin Yao,1,* Bowen Tian,1,* Zhifeng Zhao,3 Yanrong Wang,4 Xiaoliang Li,5 Dingding Jin,6 Xiaoran Yang7
1Department of Gastrointestinal Surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 2Medical Image Center, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 3Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an, 710032, People’s Republic of China; 4Department of Neurology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 5Department of Gastrointestinal Surgery, Xi’an International Medical Center Hospital, Xi’an, 710119, People’s Republic of China; 6Department of General Surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 7Department of Otolaryngology, Head and Neck surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Dingding Jin, Department of General surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, 255 Zhengyuan North Street, Jinfeng District, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China, Email 13895017577@163.com Xiaoran Yang, Department of Otolaryngology, head and neck surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, 255 Zhengyuan North Street, Jinfeng District, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China, Email Yangxr@nxmu.edu.cn
Purpose: This study investigated fluoxetine (FLX) effects on chronic unpredictable mild stress (CUMS)-induced depression and constipation, and to explore the potential synergistic benefits of combining FLX with butyrate supplementation.
Methods: A mouse model of CUMS and functional constipation (FC) was established. Behavioral assessments, fecal parameters, colonic transit time, and histological analysis were performed. Serotonin signaling, gastrointestinal hormones, intestinal barrier function, and inflammatory markers were measured. Gut microbiota composition was assessed using 16S rRNA sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified by gas chromatography-mass spectrometry.
Results: FLX significantly alleviated depressive-like behaviors (40% reduction in immobility time) and improved gastrointestinal motility (35% increase in fecal pellet output) in CUMS-FC mice. FLX restored serotonin signaling (2.5-fold increase in 5-HT levels), enhanced intestinal barrier integrity (60% upregulation of ZO-1/Occludin), and increased gut microbial diversity (Shannon index increased by 30%). FLX elevated butyrate-producing bacteria and fecal butyrate levels by 45%. Notably, the novel FLX-butyrate combination produced synergistic effects, achieving 65% improvement in gut motility, 70% reduction in pro-inflammatory cytokines (IL-1β, TNF-α, IL-6), and 80% restoration of intestinal barrier function compared to FLX alone.
Conclusion: FLX alleviates CUMS-induced depression and constipation through restoring serotonin signaling, modulating gut microbiota toward SCFA production, and improving intestinal barrier function. The novel synergistic enhancement achieved by FLX-butyrate combination demonstrates superior therapeutic efficacy, highlighting its potential as an innovative dual-targeting strategy for gut-brain axis disorders.
Keywords: fluoxetine, butyrate, CUMS, constipation, gut-brain axis
1Department of Gastrointestinal Surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 2Medical Image Center, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 3Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an, 710032, People’s Republic of China; 4Department of Neurology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 5Department of Gastrointestinal Surgery, Xi’an International Medical Center Hospital, Xi’an, 710119, People’s Republic of China; 6Department of General Surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China; 7Department of Otolaryngology, Head and Neck surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Dingding Jin, Department of General surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, 255 Zhengyuan North Street, Jinfeng District, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China, Email 13895017577@163.com Xiaoran Yang, Department of Otolaryngology, head and neck surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, 255 Zhengyuan North Street, Jinfeng District, Yinchuan, Ningxia Hui Autonomous Region, 750002, People’s Republic of China, Email Yangxr@nxmu.edu.cn
Purpose: This study investigated fluoxetine (FLX) effects on chronic unpredictable mild stress (CUMS)-induced depression and constipation, and to explore the potential synergistic benefits of combining FLX with butyrate supplementation.
Methods: A mouse model of CUMS and functional constipation (FC) was established. Behavioral assessments, fecal parameters, colonic transit time, and histological analysis were performed. Serotonin signaling, gastrointestinal hormones, intestinal barrier function, and inflammatory markers were measured. Gut microbiota composition was assessed using 16S rRNA sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified by gas chromatography-mass spectrometry.
Results: FLX significantly alleviated depressive-like behaviors (40% reduction in immobility time) and improved gastrointestinal motility (35% increase in fecal pellet output) in CUMS-FC mice. FLX restored serotonin signaling (2.5-fold increase in 5-HT levels), enhanced intestinal barrier integrity (60% upregulation of ZO-1/Occludin), and increased gut microbial diversity (Shannon index increased by 30%). FLX elevated butyrate-producing bacteria and fecal butyrate levels by 45%. Notably, the novel FLX-butyrate combination produced synergistic effects, achieving 65% improvement in gut motility, 70% reduction in pro-inflammatory cytokines (IL-1β, TNF-α, IL-6), and 80% restoration of intestinal barrier function compared to FLX alone.
Conclusion: FLX alleviates CUMS-induced depression and constipation through restoring serotonin signaling, modulating gut microbiota toward SCFA production, and improving intestinal barrier function. The novel synergistic enhancement achieved by FLX-butyrate combination demonstrates superior therapeutic efficacy, highlighting its potential as an innovative dual-targeting strategy for gut-brain axis disorders.
Keywords: fluoxetine, butyrate, CUMS, constipation, gut-brain axis