A microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression reveals physiological characteristics similar to depression

Wenxin Wang, Yiyuan Liu, Zhikai Yao, Dengbo Chen, Yue Tang, Jingwei Cui, Jiangjiang Zhang, Hong Liu*, Zikai Hao*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

摘要

The diverse commensal microbiome of the human intestine has been considered to play a central role in depression. However, no host-microbiota co-culture system has been developed for depression, which hinders the controlled study of the interaction between depression and gut microbiota. We designed and manufactured a microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression (depression-on-gut-chip, DoGC), which enables the extended co-culture of viable aerobic human intestinal epithelial cells and anaerobic gut microbiota, and allows the direct study of interactions between human gut microbiota and depression. We introduced representative gut microbiota from individuals with depression into our constructed DoGC model, successfully recapitulating the gut microbiota structure of depressed patients. This further led to the manifestation of physiological characteristics resembling depression, such as reduced gut barrier function, chronic low-grade inflammatory responses and decreased neurotransmitter 5-HT levels. Metabolome analysis of substances in the DoGC revealed a significant increase in lipopolysaccharides and tyrosine, while hyodeoxycholic acid, l-proline and l-threonine were significantly reduced, indicating the occurrence of depression. The proposed DoGC can serve as an effective platform for studying the gut microbiota of patients with depression, providing important cues for their roles in the pathology of this condition and acting as a powerful tool for personalized medicine.

源语言英语
页(从-至)2537-2550
页数14
期刊Lab on a Chip
24
9
DOI
出版状态已出版 - 4 4月 2024

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