Modulation of Gut Microbiota Combined with Upregulation of Intestinal Tight Junction Explains Anti-Inflammatory Effect of Corylin on Colitis-Associated Cancer in Mice

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Mar 10

PMID 35269806

Authors

Zi-Yu Chang

Hsuan-Miao Liu

Yann-Lii Leu

Chung-Hua Hsu

Tzung-Yan Lee

Affiliations

Soon will be listed here.

Abstract

Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The results showed corylin could improved the survival rate and colon length, maintained body weight, and ameliorated the inflammatory response in the colon. Then, we further identified the possible antitumor effects after 30-day treatment of corylin on an azoxymethane (AOM)/DSS-induced CAC mouse model. Biomarkers associated with inflammation, the colon tissue barrier, macrophage polarization (CD11c, CCR7, CD163, and CD206), and microbiota dysbiosis were monitored in the AOM/DSS group versus corylin groups. Corylin downregulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) mRNA expression and inflammatory signaling-associated markers (TLR4, MyD88, AP-1, CD11b, and F4/80). In addition, a colon barrier experiment revealed that epithelial cell proliferation of the mucus layer (Lgr5, Cyclin D1, and Olfm4) was downregulated and tight junction proteins (claudin-1 and ZO-1) were upregulated. Furthermore, the / ratio changed with corylin intervention, and the microbial diversity and community richness of the AOM/DSS mice were improved by corylin. The comparative analysis of gut microbiota revealed that , , , , and were significantly increased but , , , and decreased after corylin treatment. Altogether, corylin administration showed cancer-ameliorating effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Therefore, corylin could be a novel, potential health-protective, natural agent against CAC.

Citing Articles

MiCML: a causal machine learning cloud platform for the analysis of treatment effects using microbiome profiles.

Koh H, Kim J, Jang H BioData Min. 2025; 18(1):10.

PMID: 39885552 PMC: 11783787. DOI: 10.1186/s13040-025-00422-3.

Cecropin AD ameliorates pneumonia and intestinal injury in mice with mycoplasma pneumoniae by mediating gut microbiota.

Li B, Liu M, Du W, Wang S, Xu Z, Zhang X BMC Vet Res. 2025; 21(1):39.

PMID: 39881281 PMC: 11776147. DOI: 10.1186/s12917-025-04500-w.

Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria.

Beauchemin E, Hunter C, Maurice C mSphere. 2024; 10(1):e0082524.

PMID: 39723822 PMC: 11774032. DOI: 10.1128/msphere.00825-24.

Targeting the gut microbiota: a new strategy for colorectal cancer treatment.

Hu Y, Zhou P, Deng K, Zhou Y, Hu K J Transl Med. 2024; 22(1):915.

PMID: 39379983 PMC: 11460241. DOI: 10.1186/s12967-024-05671-0.

and HKL suspension ameliorate DSS-induced ulcerative colitis in mice by improving the intestinal barrier inhibiting the NLRP3 inflammasome and pathogenic bacteria.

Zhu J, Wang H, Aisikaer M, Yisimayili Z, Yang T, Zhou W Heliyon. 2024; 10(12):e33053.

PMID: 39027449 PMC: 11254534. DOI: 10.1016/j.heliyon.2024.e33053.

References

Cerf-Bensussan N, Gaboriau-Routhiau V . The immune system and the gut microbiota: friends or foes?. Nat Rev Immunol. 2010; 10(10):735-44. DOI: 10.1038/nri2850. View

Pilling D, Fan T, Huang D, Kaul B, Gomer R . Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts. PLoS One. 2009; 4(10):e7475. PMC: 2759556. DOI: 10.1371/journal.pone.0007475. View

Stojanov S, Berlec A, Strukelj B . The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms. 2020; 8(11). PMC: 7692443. DOI: 10.3390/microorganisms8111715. View

Murray P . Macrophage Polarization. Annu Rev Physiol. 2016; 79:541-566. DOI: 10.1146/annurev-physiol-022516-034339. View

Wu S, Hu R, Nakano H, Chen K, Liu M, He X . Modulation of Gut Microbiota by L. Berry Polyphenols in a Mouse Model of Fatty Liver Induced by High Fat Diet. Molecules. 2018; 23(12). PMC: 6321169. DOI: 10.3390/molecules23123213. View

Genaro S, de Souza Reis L, Reis S, Socca E, Favaro W . Probiotic supplementation attenuates the aggressiveness of chemically induced colorectal tumor in rats. Life Sci. 2019; 237:116895. DOI: 10.1016/j.lfs.2019.116895. View

Wu Y, Jiao N, Zhu R, Zhang Y, Wu D, Wang A . Identification of microbial markers across populations in early detection of colorectal cancer. Nat Commun. 2021; 12(1):3063. PMC: 8144394. DOI: 10.1038/s41467-021-23265-y. View

Zhang C, Li S, Yang L, Huang P, Li W, Wang S . Structural modulation of gut microbiota in life-long calorie-restricted mice. Nat Commun. 2013; 4:2163. PMC: 3717500. DOI: 10.1038/ncomms3163. View

Jurjus A, Eid A, Al Kattar S, Zeenny M, Gerges-Geagea A, Haydar H . Inflammatory bowel disease, colorectal cancer and type 2 diabetes mellitus: The links. BBA Clin. 2016; 5:16-24. PMC: 4802401. DOI: 10.1016/j.bbacli.2015.11.002. View

10.

Ozato N, Saito S, Yamaguchi T, Katashima M, Tokuda I, Sawada K . genus associated with visceral fat accumulation in adults 20-76 years of age. NPJ Biofilms Microbiomes. 2019; 5(1):28. PMC: 6778088. DOI: 10.1038/s41522-019-0101-x. View

11.

Kather J, Halama N . Harnessing the innate immune system and local immunological microenvironment to treat colorectal cancer. Br J Cancer. 2019; 120(9):871-882. PMC: 6734657. DOI: 10.1038/s41416-019-0441-6. View

12.

Peterson L, Artis D . Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014; 14(3):141-53. DOI: 10.1038/nri3608. View

13.

Chen C, Chen C, Shieh T, Hsueh C, Wang S, Leu Y . Corylin Suppresses Hepatocellular Carcinoma Progression via the Inhibition of Epithelial-Mesenchymal Transition, Mediated by Long Noncoding RNA GAS5. Int J Mol Sci. 2018; 19(2). PMC: 5855602. DOI: 10.3390/ijms19020380. View

14.

Chen C, Kuo C, Leu Y, Wang S . Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and β3-AR activation. Pharmacol Res. 2020; 164:105291. DOI: 10.1016/j.phrs.2020.105291. View

15.

Tsukita S, Furuse M, Itoh M . Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001; 2(4):285-93. DOI: 10.1038/35067088. View

16.

Dicksved J, Halfvarson J, Rosenquist M, Jarnerot G, Tysk C, Apajalahti J . Molecular analysis of the gut microbiota of identical twins with Crohn's disease. ISME J. 2008; 2(7):716-27. DOI: 10.1038/ismej.2008.37. View

17.

Wrighton K, Thomas B, Sharon I, Miller C, Castelle C, VerBerkmoes N . Fermentation, hydrogen, and sulfur metabolism in multiple uncultivated bacterial phyla. Science. 2012; 337(6102):1661-5. DOI: 10.1126/science.1224041. View

18.

Hunter M, Wang A, Parhar K, Johnston M, van Rooijen N, Beck P . In vitro-derived alternatively activated macrophages reduce colonic inflammation in mice. Gastroenterology. 2010; 138(4):1395-405. DOI: 10.1053/j.gastro.2009.12.041. View

19.

Hu C, Xiao K, Luan Z, Song J . Early weaning increases intestinal permeability, alters expression of cytokine and tight junction proteins, and activates mitogen-activated protein kinases in pigs. J Anim Sci. 2012; 91(3):1094-101. DOI: 10.2527/jas.2012-5796. View

20.

Furuse M . Molecular basis of the core structure of tight junctions. Cold Spring Harb Perspect Biol. 2010; 2(1):a002907. PMC: 2827901. DOI: 10.1101/cshperspect.a002907. View