It's widely understood that the microbiome—especially microbes found in the mouth and the gut—can have a profound effect on health. In a study publishing in the Cell Press journal Cell Host & Microbe on August 20, researchers report that by analyzing the make-up of oral microbes, they may be able to detect signals associated with gastric (stomach) and colorectal cancer. These findings could lead to the development of new, less-invasive screening tests for gastrointestinal cancers.
"Many species of microbes associated with the mouth are also present in the gut and may flourish there," says co-corresponding and lead author Jihyun F. Kim of Yonsei University in Seoul. "These observations made us wonder whether oral microbes reach and persist in the gastrointestinal tract differently in people with cancer."
To conduct the study, the researchers recruited 507 volunteers to donate both oral and fecal samples, using a highly standardized collection process. The cohort included 129 healthy individuals; 215 people with metabolic disorders such as metabolic syndrome, hypertension, hyperlipidemia, and type 2 diabetes; 77 people with gastric cancer; and 86 people with colorectal cancer. For the volunteers with cancer, samples were collected before the start of any treatment.
The team used gene sequencing to create what they called a mouth-to-feces (MF) index, which measures the extent to which identical microbial sequence variants are found in oral and fecal samples from the same person. They then evaluated how well the MF index could distinguish cancer patients from healthy individuals. The analysis revealed distinct signatures in people with gastric or colorectal cancer.
The findings were more nuanced than a simple cancer-versus-healthy comparison. The MF index was significantly elevated in patients with gastric or colorectal cancer but not in people with metabolic disorders. After accounting for alcohol consumption, regular exercise, and BMI, the association remained robust for both gastric and colorectal cancers.
"The presence of oral-associated bacteria in the gut of patients with cancer was not entirely unexpected," says co-corresponding author Sun Ha Jee, also of Yonsei University. "What we had not fully anticipated was how the signal varied across disease groups, how much of it could be detected in oral samples alone, and how strongly it depended on the way microbial features were represented."
The team also compared the signatures found in the cancer patients to results from fecal occult blood tests, a standard colorectal cancer screening tool that analyzes stool samples. They found higher sensitivity with the oral samples, which were collected by a simple mouth rinse.
"It was notable that cancer-related information could be recovered from oral samples alone," adds co-corresponding author Yong Chan Lee of Yonsei University College of Medicine. "Although only a small fraction of oral bacterial variants were also detected in the gut, models built using only these oral features could distinguish patients with cancer from healthy individuals across several independent cohorts."
The researchers are planning a study to prospectively validate the findings in people who do not already have a cancer diagnosis. They also plan to incorporate higher-resolution metagenome sequencing. Additional research will look at causality: whether increased mouth-gut microbial sharing contributes to cancer development, whether cancer creates conditions that allow oral bacteria to remain in the gastrointestinal tract, or both.
"Before any of this could be used in practice, it would need to go through clinical studies in real screening populations," says co-corresponding author Tae Il Kim, also of Yonsei University College of Medicine.
If the findings are validated with further studies, the researchers say the next step would be developing a non-invasive test. An oral-rinse test in particular would be easy to collect and generally less burdensome than a stool test, the authors note, and could help identify people who should be prioritized for established diagnostic procedures such as upper endoscopy or colonoscopy.
In the longer term, combining microbial patterns with genetics, lifestyle, and clinical outcomes may help explain why oral microbes persist more readily in some people than in others and may improve individualized risk prediction.
