2. Academic Validation
  3. Carvacrol attenuates mucosal barrier impairment and tumorigenesis by regulating gut microbiome

Carvacrol attenuates mucosal barrier impairment and tumorigenesis by regulating gut microbiome

  • Transl Oncol. 2025 Aug:58:102431. doi: 10.1016/j.tranon.2025.102431.
Yating Fan 1,  Ye Chen 1,  Hua Yang 2,  Na Chen 1,  Xiangshuai Gu 1,  Xiaoliang Feng 1,  Chao Fang 3,  Yuan Yin 4,  Hongxin Deng 5,  Lei Dai 6
Affiliations

Affiliations

  • 1 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 2 Huidong General Surgery Department of Zigong Fourth People's Hospita, Zigong, 643000, China.
  • 3 Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • 4 Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: yinyuan10@hotmail.com.
  • 5 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: denghongx@scu.edu.cn.
  • 6 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: dailei2016@scu.edu.cn.
PMID: 40424934 DOI: 10.1016/j.tranon.2025.102431
Abstract

Colitis-associated colorectal Cancer (CAC), which stems from inflammatory bowel disease (IBD), exhibits a high mortality rate. Chronic inflammation can drive the development of colorectal Cancer via diverse mechanisms; however, proteomic-level studies in this regard are currently scarce. The chemical drugs conventionally employed for treating IBD carry significant side effects, accentuating the exigency for novel therapeutic agents. We focused on carvacrol, a traditional Chinese medicine-derived monoterpene phenol with anti-inflammatory and antioxidant traits, though its role in colitis and CAC was unclear. Employing TMT-based proteomics, we identified the oxidative stress pathway as crucial in CAC, with ALB, ADAM10, and APCDD1 (hub genes) being vital. Using DSS and AOM/DSS mouse models, carvacrol significantly restored colonic length (p < 0.01) and re-established key tight junction proteins like ZO-1. It also downregulated mRNA levels of inflammatory mediators such as iNOS and IL-6. Moreover, 16S rRNA Sequencing and fluorescence in situ hybridization (FISH) assays indicated that the potential mechanism might be ascribed to carvacrol's modulation of the abundance of specific microbiota, such as Lactobacillus, Escherichia coli/Shigella, and Lachnoclostridium. In subsequent investigations, we ascertained that carvacrol exerted remarkable efficacy in the AOM/DSS models, as it markedly reduced the number of colonic tumors (p < 0.05) and concurrently suppressed the disease activity index scores (p < 0.05). These results jointly suggest its prospective role in thwarting the progression of colitis-associated colorectal Cancer. Collectively, our study substantiates that carvacrol efficiently safeguards the mucosal barrier and curbs tumorigenesis, potentially via the modulation of gut microbiota.

Keywords

Carvacrol; Colitis; Colorectal cancer; Intestinal microbiota; Proteomic analysis.

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