Role of the gut microbiome in causing, detecting and treating coloretal cancer.


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Paul O'Toole1
1School of Microbiology and APC Microbiome Inst

Abstract

Role of the gut microbiome in causing, detecting and treating colorectal cancer.Prof. Paul W. O’Toole, School of Microbiology & APC Microbiome Institute, University College Cork, Ireland. Alterations in gut microbiota composition and function have been linked to various diseases including cancer. Colorectal cancer (CRC) could be caused by microbes affecting inflammation, cell death or by increasing mutation frequency in susceptible individuals. Thus, the microbiota would act as an additional environmental risk factor for cancer. Supporting this theory, CRC-associated microbes can accelerate cancer in animal models, but definitive causative links in humans have yet to be established. Regardless of the mechanisms involved, CRC-associated microbiota composition differs from those in healthy subjects and we showed that they are linked with distinct mucosal gene-expression profiles. Furthermore, several labs have reported that the altered microbiota on colonic biopsies or in stool samples can be used to detect CRC. Because the CRC microbiota often contains bacteria from the oral cavity, we tested oral swabs for CRC detection. The oral microbiota data allowed us to identify people with polyps or cancer from healthy controls, and combining oral data with faecal microbiota data led to significantly improved sensitivity and specificity.An exciting way of treating some cancer types is to administer immune checkpoint inhibitors, monoclonal antibodies or small molecules that prevent inhibition of T-cell activation, allowing the immune system to fight the cancer. Recent data from animal models and some human studies has shown that whether immune check-point inhibitors are clinically effective or not depends on the patient’s gut microbiota composition. This relates to how the microbiota co-regulates T-cell activation. Furthermore, whether the patient experiences colitis or not, which happens in a minority of those treated and requires therapy withdrawal, also appears to be a feature of their gut microbiota composition. Overall, the gut microbiota is a promising (and targetable) risk factor for colorectal cancer, a potential diagnostic for colorectal cancer, and a modifiable modulator of cancer immunotherapy.