What is already known on this topic
Radiotherapy is a cancer treatment that uses high doses of radiation to kill cancer cells. While radiotherapy has saved countless lives, its efficacy varies between cancer patients, and the treatment has several side effects that impair the quality of life of patients.

What this research adds
Working in a mouse model of colorectal cancer, researchers have found that alterations of the mouth microbiota can change the bacterial composition within tumors. Oral microbes also appear to be associated with radiation-induced intestinal damage mediated by gut bacteria. What’s more, mouth-dwelling Fusobacterium nucleatum can migrate to colorectal tumors and impair the efficacy of radiotherapy. Giving mice the antibiotic metronidazole, which kills F. nucleatum, reduces these effects.

Conclusions
The findings suggest that the mouth microbiota, together with its intestinal counterpart, can influence the efficacy of radiotherapy for colorectal cancer.

Radiotherapy is a cancer treatment that uses high doses of radiation to kill cancer cells. While radiotherapy has saved countless lives, its efficacy varies between cancer patients, and the treatment has several side effects that impair the quality of life of patients. Now, a study in mice shows that the mouth microbiota, together with its intestinal counterpart, can influence the efficacy of radiotherapy for colorectal cancer.

The findings, published in Cell Reports, offer insights into the role of the mouth microbiota in reducing the efficacy of radiotherapy. They also suggest that specific oral microbes can be used as biomarkers and targets for the diagnosis and treatment of colorectal cancer.

Previous studies have shown that several oral bacteria are associated with colorectal cancer, indicating that some microbes may interact to promote the development of disorders of the digestive tract. In particular, Fusobacterium nucleatum — a microbe that resides in the oral cavity and can cause periodontal diseases — has been shown to cause gut inflammation and contribute to the development and progression of colorectal cancer

F. nucleatum can persist in tumors from people with recurrent rectal cancer following chemo-radiotherapy, but it’s unclear whether this and other mouth bacteria influence the efficacy of radiotherapy for the treatment of colorectal cancer.

To explore the effects of the mouth microbiota on this type of radiotherapy, researchers led by Saijun Fan and Ming Cui at the Chinese Academy of Medical Sciences and Peking Union Medical College analyzed the microbiota of mice with colorectal cancer and of healthy controls.

Therapy efficacy

The oral microbiota of sick mice harbored more bacterial species than that of healthy mice. Compared to the oral microbiota of animals with mild disease, that of severely sick mice had lower abundances of Bacteroides, Gemella, and Streptococcus

To examine the effects of oral bacteria on the efficacy of radiotherapy for colorectal cancer, the team altered the mouth microbiota of mice through oral microbiota transplantation and then exposed the animals to radiation. Alterations of the oral microbiota reduced the length of the colon and impaired the cancer-killing effects of radiation. They also worsened radiation-induced damage of the digestive tract and increased the production of inflammatory immune molecules.

In particular, oral F. nucleatum elicited resistance to radiotherapy for colorectal cancer, and higher levels of F. nucleatum in the oral cavity were associated with an enrichment of this microbe at colorectal cancer sites. Increased levels of F. nucleatum worsened gut inflammation and reduced the integrity of the intestinal lining, the researchers found.

Microbial biomarker

Next, the team treated mice with the antibiotic metronidazole to kill Fusobacterium in the digestive tract. Metronidazole treatment reduced the resistance to radiotherapy associated with oral microbiota alterations, the researchers found.

Further experiments suggested that mouth microbes can migrate to the lower digestive tract, where they worsen the radiation-induced intestinal damage mediated by gut microbes. “Our observations demonstrate that the oral-gut microbiota axis contributes to the prognosis of radiation-induced [gastrointestinal] injuries,” the researchers say.

The findings indicate that oral F. nucleatum may colonize sites of colorectal cancer and contribute to radiotherapy resistance. However, this effect can be blocked by metronidazole treatment. “Oral F. nucleatum may be used as a potential biomarker and target for the diagnosis and treatment of [colorectal cancer] in combination with good oral hygiene practice and the use of appropriate antibiotics,” the authors say.