Journal Article Epublish
PubMed: 42370185 DOI: 10.7150/thno.132241
Honeysuckle-derived nanovesicles alleviate inflammatory bowel disease-associated neuropsychiatric disorders via the gut-brain axis.
Theranostics 16(13):7419-7441
Authors: Ailin Wu, Qin Chu, Le Ding, Yan Zeng, Liqiang Shao, Yuanyuan Wang, Yuanhao Zhou, Weijiao Fan, Xin Zhang, Jianwei Wang, Jie Wang, Shunyuan Guo, Ketao Jin, Xiaoru Chang, Xiaozhou Mou
Affiliations
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. College of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
- Department of Neurology, Center for Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
- College of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
- EVitalBio (Hangzhou) Co. Ltd, Hangzhou, Zhejiang, China.
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University. Hangzhou, Zhejiang 310003, China.
Abstract
RATIONALE
Inflammatory bowel disease (IBD) is frequently accompanied by anxiety and depression, yet effective therapies targeting both intestinal inflammation and neuropsychiatric symptoms remain limited. This study aimed to investigate whether honeysuckle-derived nanovesicles (HNVs) could alleviate IBD-related affective disturbances by modulating the microbial-gut-brain axis (MGBA).
METHODS
A chronic colitis mouse model was established using dextran sulfate sodium (DSS). Mice were treated orally with HNVs, and anxiety- and depression-like behaviors were evaluated using behavioral assays. Intestinal barrier integrity, gut microbiota composition, systemic immune responses, proinflammatory cytokine production, hippocampal immune infiltration, 5-hydroxytryptamine (5-HT) biosynthesis and metabolism, and activation of the BDNF/TrkB/GSK3β signaling pathway were assessed using histological, microbiological, immunological, biochemical, and molecular analyses.
RESULTS
Oral administration of HNVs markedly attenuated anxiety- and depression-like behaviors in mice with chronic colitis. HNV treatment preserved intestinal barrier integrity, reshaped the gut microbial community, modulated systemic immune responses, reduced proinflammatory cytokine production and hippocampal inflammatory infiltration, and regulated 5-HT biosynthesis and metabolic pathways. These effects were associated with restoration of intestinal and neural homeostasis and activation of the BDNF/TrkB/GSK3β signaling cascade.
CONCLUSIONS
HNVs alleviated IBD-related affective disturbances in experimental chronic colitis by regulating the MGBA, suppressing inflammation, modulating 5-HT metabolism, and restoring intestinal and neural homeostasis. These findings support HNVs as a potential natural nanotherapeutic strategy for the integrated management of intestinal inflammation and associated neuropsychiatric comorbidities.
MeSH
Cytokines, Depression, Nanomedicine, Colitis, Homeostasis, Brain, Inflammatory Bowel Diseases, Immunity, Therapeutics, Microbiota