Issue 13, 2025

Lycopene regulates intestinal dysmotility and behavioral disorders by regulating enteric neurons and the cholinergic system

Abstract

Gut dysmotility is a prevalent gastrointestinal disorder characterized by disrupted defecation and often accompanied by depression and anxiety. Lycopene (LYC) is a type of carotenoid with strong antioxidant and anti-inflammatory properties. However, the effects of LYC on gut dysmotility and related behavioral disorders remain elusive. Herein, we found that 100 mg kg−1 d−1 LYC notably improved the gut transit time and intestinal transit rate as well as concurrently alleviated depression- and anxiety-like behaviors in a diphenoxylate (Dip, 5 mg kg−1 d−1)-induced constipated mouse model. LYC pretreatment enhanced gut barrier integrity and short-chain fatty acid (SCFA) production as well as rebalanced gut microbiota homeostasis by enriching beneficial bacteria, including Bifidobacterium and Akkermansia. Furthermore, LYC restored enteric neuronal function, as evidenced by increased HuC/D and Tuj1 expression as well as balanced neurotransmitter levels. Brain transcriptomics results suggest that LYC regulates the cholinergic synapse pathway and increases acetylcholine (Ach) content in the brain, which is associated with the alleviation of neuroinflammation. In summary, this study offers insights into functional dietary component-based nutritional strategies that target gut dysmotility comorbid behavioral dysfunction.

Graphical abstract: Lycopene regulates intestinal dysmotility and behavioral disorders by regulating enteric neurons and the cholinergic system

Supplementary files

Article information

Article type
Paper
Submitted
03 Jan 2025
Accepted
25 May 2025
First published
26 May 2025

Food Funct., 2025,16, 5363-5379

Lycopene regulates intestinal dysmotility and behavioral disorders by regulating enteric neurons and the cholinergic system

D. Wang, S. Jiao, Q. Guo, M. Zhou, W. Ren, Y. Zhao, D. Li, W. Yang, S. Dai, Y. Pei, D. Xiao, X. Liu, C. Xiao and B. Zhao, Food Funct., 2025, 16, 5363 DOI: 10.1039/D5FO00039D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements