Dose-dependent effects of capsaicin on intestinal morphology and microbiota composition in mice: Structural, immunohistochemical, and microbial insights

Vet World Vol.18 June-2025 Article - 28

Research Article

Veterinary World, 18(6): 1703-1714

https://doi.org/10.14202/vetworld.2025.1703-1714

Kai Li¹

, Jianghai Xu^1,2

, Siying Chen¹, Aifei Du¹

, Shaohua Feng¹, Shibin Yuan^1,3,4

, and Bangyuan Wu^1,3,4

1. College of Life Sciences, China West Normal University, Nanchong, 637000, Sichuan, China.

2. Yucai School Attached to Sichuan Chengdu No. 7 High School, Chengdu, 610021, Sichuan, China.

3. Key Laboratory of Southwest China Wildlife Resources Conservation, Ministry of Education, Nanchong, Sichuan, 637000, China.

4. Nanchong Key Laboratory of Wildlife Nutritional Ecology and Disease Prevention and Control, Nanchong, 637000, Sichuan, China.

Background and Aim: Capsaicin (CAP), the pungent component of chili peppers, possesses diverse bioactive properties, including antioxidant, anti-inflammatory, and antimicrobial effects. However, its impact on gastrointestinal integrity and microbial ecology remains dose-dependent and incompletely understood. This study aimed to investigate the effects of varying CAP doses on intestinal morphology, tight junction protein expression, goblet cell density, mucosal injury markers, and gut microbiota composition in mice.

Materials and Methods: Seventy-five male Kunming mice were randomly assigned to five groups (n = 15/group): Normal control, vehicle control (dimethyl sulfoxide), low-dose CAP (5 mg/kg), medium-dose (15 mg/kg), and high-dose (20 mg/kg). Mice received oral gavage every other day for 14 days. Histological assessments (H&E and Alcian Blue-Periodic Acid–Schiff staining), enzyme-linked immunosorbent assays for diamine oxidase, fatty acid-binding protein 2, and plasma endotoxin as well as immunohistochemistry for ZO-1, Claudin-1, and Occludin, and 16S rRNA sequencing were employed to evaluate structural and microbial changes.

Results: Low-dose CAP significantly enhanced villus height, reduced crypt depth, and elevated the villus-to-crypt ratio across all intestinal segments (p < 0.05). Tight junction protein expression and goblet cell counts were highest in the low-dose group, suggesting mucosal protection. In contrast, medium and high-dose CAP induced epithelial damage, villus atrophy, and downregulation of junctional proteins. Microbiota analysis revealed the suppression of Proteobacteria and the expansion of Firmicutes in the medium- and high-dose groups. All CAP doses stimulated microbial biosynthesis of cofactors, vitamins, and electron carriers, with enhanced alpha diversity at higher doses.

Conclusion: CAP exhibits a biphasic effect on intestinal physiology. While low-dose administration supports mucosal integrity and promotes beneficial microbial functions, higher doses disrupt epithelial architecture and induce dysbiosis. These findings underscore the importance of dose consideration in CAP’s dietary and therapeutic applications, providing mechanistic insights into its gut-mediated effects.

Keywords: capsaicin, dose-response, goblet cells, gut microbiota, intestinal barrier, mucosal injury, tight junction proteins.

How to cite this article: : Li K, Xu J, Chen S, Du A, Feng S, Yuan S, and Wu B. (2025) Dose-dependent effects of capsaicin on intestinal morphology and microbiota composition in mice: Structural, immunohistochemical, and microbial insights, Veterinary World, 18(6): 1703–1714.

Received: 30-04-2025 Accepted: 29-05-2025 Published online: 26-06-2025

Corresponding author: Bangyuan Wu and Shibin Yuan E-mail: wubangyuan2008@163.com and yshibin1020@cwnu.edu.cn

DOI: 10.14202/vetworld.2025.1703-1714

Copyright: Li, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.