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Updated: Oct 27, 2026
A Method to Define the Effects of Environmental Enrichment on Colon Microbiome Biodiversity in a Mouse Colon Tumor Model
Published on: February 28, 2018
Longitudinal Gut Microbiota Changes in Mouse Models of Chronic Colitis, Colitis-Associated Cancer, and
Juncong Hu1, Anqi Yang1, Xinru Li1
1Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
Background:
Gut microbiota contributes to intestinal pathologies, but microbial and metabolic differences distinguishing inflammation-associated tumorigenesis from chronic colitis remain unclear. This study mapped stage-dependent microbiota dynamics and metabolic perturbations across three independent mouse models: chronic ulcerative colitis (CUC), AOM/DSS-induced colitis-associated cancer (CAC), and chemotherapy-induced diarrhea (CID).
Methods:
CUC, CAC, and CID were induced by cyclic DSS, AOM/DSS, and CPT-11, respectively. Disease progression was monitored via endoscopy, histopathology, and Disease Activity Index. Gut microbiota was profiled by 16S rRNA sequencing across three stages (R01-R03); metabolic and inflammatory changes were assessed by RT-qPCR and metabolite assays. Mediation analysis was used to explore whether the associations between microbial abundance and host metabolic/inflammatory markers were statistically consistent with an indirect pathway.
Results:
CID showed distinct acute transient injury and a unique microbiota structure separate from CUC/CAC. In CUC and CAC, microbiota restructured stage-dependently: beneficial genera (Akkermansia) declined, while pathobionts (norank_o_Clostridia_UCG-014) increased. CAC showed upregulation of glycolysis genes (HK2, PKM2, LDHA, Glut1) together with elevated colonic lactate concentrations, and elevated colonic concentrations of the pro-inflammatory cytokines IL-17A and IL-22, indicating distinct colonic metabolic and inflammatory changes associated with gut dysbiosis. Mediation analysis showed that norank_o__Clostridia_UCG-014 showed consistently positive indirect effects, irrespective of the glycolytic enzyme and lactate enantiomer examined; and Allobaculum had a consistently positive indirect effect on both IL-17A and IL-22.
Conclusion:
These findings reveal distinct stage-specific microbial and metabolic signatures distinguishing AOM/DSS tumor-bearing mice from nonneoplastic chronic colitis and acute chemotherapy intestinal injury.
