Tumor microbiota identified as predictors of prognosis in gastrointestinal cancers

Microbes inside cancerous tumors can influence the spread of disease and the effectiveness of treatment. Those roles make them appealing targets for new therapies and offer ways to better predict risk. Tumor microbiota-based tools could help identify high-risk patients and people most susceptible to metastases, and possibly be used to improve prognosis tools, reported a group of microbiologists at Nankai University in Tianjin, China. 

This week in Microbiology Spectrum, the researchers described a core group of 15 bacterial genera, found in 6 types of gastrointestinal (GI) tumors, that predicts prognosis. The genera were validated across all 6 types. 

Worldwide, GI cancers account for about a quarter of new diagnoses and a third of deaths every year, and incidence rates are rising among people younger than 50. Recent studies have shown that these tumors harbor rich microbial populations, and harnessing microbial signatures offers a way to improve response to therapy, said mycologist Xingzhong Liu, Ph.D, who co-led the new study. 

"Microbiome signals inside tumors are not just bystanders," Liu said, whose research group focuses on how interactions among different microbes affect outcomes in the host. "They carry prognostic and therapeutic information that can be measured on routine tissue." 

Previous studies have found connections between individual microbes and the growth and treatment responses of specific cancer types. Staphylococcus, Lactobacillus and Enterococcus, for example, may promote the spread of breast cancer, and Escherichia coli can prevent cancer treatment from working on colon cancer cells. The new work, however, takes a wider view, linking microbial patterns to metastasis pathways across multiple cancer types known to have rich microbial populations, Liu said. "We see this model as applicable across GI tumors, pending prospective testing." 

The group analyzed 1,602 GI tumor tissue samples and 116 samples of adjacent normal tissues from a public dataset. They found consistent associations between many genera and risk and immune response. Samples with a higher abundance of Granulicella bacteria, for example, had fewer activated CD8+ T cells-an immune response-and a higher risk of metastasis. Dorea bacteria, on the other hand, were correlated with a protective immune response and lower risk of metastasis. 

The researchers used the findings to design a microbiota-based risk score that predicted worse survival and higher likelihood of metastasis in high-risk patients, as well as response to some immunotherapies. The next step is to validate the findings in further studies and to better understand the mechanisms underlying these connections. Eventually, Liu said, they hope to produce a decision-making tool that augments existing methods. 

Our model doesn't replace staging or genomic markers but offers a complementary layer that can help identify high-risk and metastasis-prone patients and refer for therapy selection, especially when immunotherapy may be less effective."

Xingzhong Liu, Ph.D, mycologist