Navy Dentist Lt. Benjamin Anderson (seated left) and Dental Technician Lennard Henry perform a routine procedure on a patient. Image by US Navy photo by Chief Photographer under Creative Commons 4.0 license
Two new studies from researchers at the Fred Hutchinson Cancer Center have revealed how bacteria infiltrate tumors and how they might help tumors progress and spread. The team also showed that different microbial players in the structure of a tumor microbiota (the entire collection of microbes it carries) could influence how a cancer responds to treatment.
The two articles, one published in cell reports and the other published in Naturefocus on a oral bacteria called Fusobacterium nucleatumIt has been linked to colorectal cancer. F. nucleatum it is an anaerobic commensal and a periodontal pathogen associated with a wide spectrum of human diseases.
In relation to cancer, Fusobacterium species are recovered in greater numbers in certain types of colon tumors compared to the colons of healthy individuals. F. nucleatum creates a pro-inflammatory environment conducive to tumor growth through the recruitment of tumor-infiltrating immune cells. This suggests a direct and specific carcinogenesis.
In the first research study, F. nucleatum is established as the dominant bacterial species in colorectal cancer tissue. This tissue is associated with cancer progression and a worse patient prognosis.
Based on a small molecule inhibitor screen of 1,846 bioactive compounds against a F. nucleatum isolated, the researchers found that 15 percent of the inhibitors are antineoplastic agents, including fluoropyrimidines.
An evaluation of these findings revealed that 5-fluorouracil (5-FU), a first-line chemotherapeutic for colorectal cancer, is a potent inhibitor of F. nucleatum isolates.
In addition to being potent against these undesirable microbes, 5-fluorouracil may also allow beneficial microbes to work. The researchers identified members of the intratumoral microbiota, including Escherichia coli, which are resistant to 5-fluorouracil. These E.coli The isolates can modify 5-fluorouracil and alleviate the toxicity of 5-fluorouracil towards sensitive others. F. nucleatum and human colorectal cancer epithelial cells.
East the study is titled “The cancer chemotherapeutic 5-fluorouracil is a potent inhibitor of Fusobacterium nucleatum and its activity is modified by the intratumoral microbiota.”
The second study further confirms the role of F. nucleatum. This demonstrates that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells into the bacterial regions. This was based on sequencing of the 16S rRNA gene in 44 pieces of tissue from the tumors of eleven patients.
Taken together, these data reveal that the distribution of the microbiota within a tumor is not random; instead, it is highly organized into microniches with epithelial and immune cell functions that promote cancer progression.
Gaining this understanding is important because a high load of F. nucleatum in tumors of patients with colorectal cancer, it is associated with resistance to chemotherapy, recurrence of the disease, metastasis, and poorer survival. This means that new treatment options need to be explored, and this could be influenced by disturbing the microbial balance. the second research study It is entitled “Effect of intratumoral microbiota on spatial and cellular heterogeneity in cancer”.