Bacterial Involvement in Progression and Metastasis of Colorectal Neoplasia

Abstract

While the gut microbiome is composed of numerous bacteria, specific bacteria within the gut may play a significant role in carcinogenesis, progression, and metastasis of colorectal carcinoma (CRC). Certain microbial species are known to be associated with specific cancers; however, the interrelationship between bacteria and metastasis is still enigmatic. Mounting evidence suggests that bacteria participate in cancer organotropism during solid tumor metastasis. A critical review of the literature was conducted to better characterize what is known about bacteria populating a distant site and whether a tumor depends upon the same microenvironment during or after metastasis. The processes of carcinogenesis, tumor growth and metastatic spread in the setting of bacterial infection were examined in detail. The literature was scrutinized to discover the role of the lymphatic and venous systems in tumor metastasis and how microbes affect these processes. Some bacteria have a potent ability to enhance epithelial-mesenchymal transition, a critical step in the metastatic cascade. Bacteria also can modify the microenvironment and the local immune profile at a metastatic site. Early targeted antibiotic therapy should be further investigated as a measure to prevent metastatic spread in the setting of bacterial infection.

Keywords: bacterial infection; carcinogenesis; colorectal carcinoma; epithelial–mesenchymal transition; gastrointestinal neoplasm; infectious disease; malignancy; metastasis.

Figure 1

Most common sites of metastasis of colorectal neoplasia specific tumor type. Figure created using biorender.

Figure 2

Adenoma–carcinoma sequence. Loss of tumor-suppressor gene, APC, results in hyperproliferative epithelium due to loss of cellular adhesion and increased proliferation. Further mutations of KRAS, delete in colorectal cancer (DCC), and p53 accumulate to yield carcinoma. Figure created using biorender.

Figure 3

The metastatic cascade is a stepwise process involving carcinogenesis, detachment, and invasion, intravasation and dissemination, and extravasation and proliferation at a distant site. Figure created using biorender.

Figure 4

Bacterial influence in the metastatic cascade at the primary tumor and formation of a premetastatic niche at the site of metastasis. Figure created using biorender.