# Effect of Gut Microbiota Alteration on Colorectal Cancer Progression in an In Vivo Model: Histopathological and Immunological Evaluation

## TL;DR

This study shows that gut microbiota from colorectal cancer patients worsens cancer progression in mice, affecting both tissue structure and immune responses.

## Contribution

The novel contribution is demonstrating how human gut microbiota transplantation influences CRC progression in a murine model through histopathological and immunological changes.

## Key findings

- Mice receiving CRC patient microbiota showed increased mitotic activity and dysplasia.
- FMT modulated cytokine levels like IL-1β, IL-6, and TNF-α in both healthy and CRC-derived groups.
- Human GM transplantation altered the colonic microenvironment and tumor dynamics in mice.

## Abstract

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.