Host-microbe interaction networks revealed through gut microbiota and microRNA correlation analysis in mouse models of chronic colitis and colitis-associated cancer

Abstract

Background/Aims: Gut microbiota and host microRNAs (miRNAs) are important regulators of intestinal inflammation and tumorigenesis. This study investigated dynamic changes in microbial composition, miRNA expression, and their interactions in chemically induced models of chronic colitis and colitis-associated cancer (CAC). Methods: Chronic colitis and CAC were induced in mice using dextran sodium sulfate (DSS) and DSS plus azoxymethane (AOM), respectively. Colon inflammation and tumor formation were assessed histologically and molecularly. Gut microbiota composition and miRNA expression profiles were analyzed via 16S rRNA gene sequencing and microarray, respectively. Correlation analyses between microbial genera and miRNAs were conducted using Spearman's rank correlations. Results: DSS- and AOM/DSS-treated mice exhibited weight loss, colon shortening, increased inflammation scores, and pro-inflammatory cytokine expression. Tumors were observed only in the AOM/DSS group. Microbial alpha diversity was reduced in both the DSS and AOM/DSS groups, and a beta diversity analysis revealed distinct community structures relative to controls. A LEfSe analysis identified distinct microbial genera enriched in each group, including Romboutsia, Turicibacter, Clostridium, and Akkermansia. miRNA profiling revealed several differentially expressed miRNAs, including miR-7025-5p, miR-1895, and miR-7040-5p. The correlation analysis revealed multiple significant associations between microbial taxa and miRNAs. Notably, Romboutsia showed positive correlations with several upregulated miRNAs, including miR-1895 and miR-7040-5p, and Velocimicrobium displayed negative correlations with the same miRNAs in DSS-treated mice. Additionally, Romboutsia exhibited consistent positive correlations with miR-1895 and miR-7040-5p in both the colitis and CAC models, suggesting that this taxa-miRNA pair could be involved in a common pathogenic mechanism underlying both colitis and tumorigenesis. Conclusion: Gut microbiota and host miRNA profiles are dynamically modulated in colitis and CAC, with multiple disease-specific and conserved taxa-miRNA associations. These findings support a potential role for the microbe-miRNA axis in colitis and CAC pathogenesis.