Background/Objetives: This study standardized a chemically induced colorectal cancer (CRC) model using azoxymethane (AOM) and dextran sodium sulfate (DSS) in BALB/c mice, replicating the progression from preneoplastic lesions to adenocarcinoma observed in human colorectal carcinogenesis. Methods: The CCR-AOM/DSS model was standardized in male and female BALB/c mice. Two protocols were tested. Subsequently, the positive control group was established with nine evaluation points. Tumor progression was characterized histopathologically and corroborated by methylene blue staining and scanning electron microscopy. Results: Two cycles of 2% DSS combined with a single injection of AOM (10 mg/kg) were necessary to induce adenocarcinoma in 100% of the mice, with no significant sex-based differences in tumor development. Females showed earlier tumor susceptibility under certain protocols. Inflammatory processes played a critical role in tumorigenesis, with neutrophil infiltration and fibrosis observed. Conclusions: The findings align with previous reports, emphasizing the influence of DSS cycles, molecular weight, and mouse strain on model outcomes. This standardized model provides a reliable platform for the preclinical evaluation of novel preventive and therapeutic strategies for CRC.

Background/Objectives: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, with its development influenced by diet, obesity, and gut microbiota (GM) alterations. This study aimed to evaluate the impact of human fecal microbiota transplantation (FMT) on the progression of CRC in a murine model. Methods: CRC was chemically induced in BALB/c mice using azoxymethane/dextran sulfate sodium (AOM/DSS). Mice were transferred with GM via FMT and divided into two experimental groups according to the microbiota source (healthy donors or CRC patients). A positive control group (AOM/DSS without FMT) and a negative control group (no CRC induction or FMT) were included. Clinical parameters, histopathological analyses, and cytokine profiling were performed. Results: Mice receiving FMT, particularly from CRC patients, exhibited increased mitotic activity, dysplasia, neoplastic proliferation, structural alterations in the colon, and more pronounced GALT hyperplasia. At the immunological level, both FMT groups (healthy and CRC-derived) showed modulation of IL-1β, IL-4, IL-6, IL-10, IL-17A, and TNF-α compared to the positive control. Conclusions: Human GM transplantation modulated the colonic microenvironment through histopathological and immunological changes, influencing CRC progression in this murine model. These findings highlight the role of GM in shaping CRC development and suggest that human-derived microbiota may significantly impact tumor dynamics.