Writing in The Journal of Experimental Medicine, research reveal that it is not only genetics that predispose risk of bowel cancer; showing that microbes living in the gut help drive the development of colorectal cancers.
Led by Dr Sergio Lira at the Icahn School of Medicine at Mount Sinai, New York, the research team investigated whether gut microbes have a hand in tumour development after noting that although genetic mutations can occur anywhere in the human intestine, certain types of cancer tend to develop in particular locations. This suggests that additional non-genetic factors contribute to tumour growth and dictate where pre-cancerous polyps appear, said the team.
“We show that a host-specific microbiome was associated with SPs [serrated polyps] and that alterations of the microbiota induced by antibiotic treatment or by embryo transfer rederivation markedly inhibited the formation of SPs in the cecum,” revealed Lira and colleagues.
“These results indicate that nongenetic factors contribute to the development of SPs and suggest that the development of these intestinal neoplasms in the cecum is driven by the interplay between genetic changes in the host, an inflammatory response, and a host-specific microbiota,” they concluded.
While further research is needed to confirm the identity of the cancer-promoting bacteria, the findings suggest it may be possible to reduce the risk of colorectal cancer in genetically susceptible individuals by removing certain types of gut bacteria, said the team.
Diet, cancer and the microbiota
Lira said that while genetics play an important role in cancer risk, it could be that alterations to our microbiota caused by diet and lifestyle are behind previously suggested dietary risk factors.
"In addition to genetic changes, various lifestyle-related factors, such as obesity and diet, have been linked to colorectal cancer,” Lira commented. “Some of these lifestyle factors appear to affect the types of bacteria present in the gut."
"Ultimately, understanding the interplay between genetic mutations, gut microbes, and inflammation may lead to novel diagnostics and therapies for intestinal cancer."
Research highlights
In the new study, the team used transgenic mice that expressed HB-EGF throughout the intestine but developed SPs only in the cecum.
The mice were treated with antibiotics to disrupt the populations of microbes living in their gut. This was found to prevent the formation of polyps, therefore showing that bacteria are essential for early tumour development, said the team.
“Mechanistically, development of SPs was associated with a local decrease in epithelial barrier function, bacterial invasion, production of antimicrobials, and increased expression of several inflammatory factors such as IL-17, Cxcl2, Tnf-α, and IL-1,” the team wrote. “Increased numbers of neutrophils were found within the SPs, and their depletion significantly reduced polyp growth.”
Source: The Journal of Experimental Medicine
Published online ahead of print, doi: 10.1084/jem.20131587
"Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice"
Authors: Gerold Bongers, Michelle E. Pacer, et al