Abstract
Studies in mice show that gut bacteria play a role in the formation of serrated colon polyps, benign tumors that can become malignant. Additional research is needed to understand the impact of gut bacteria on human cancers.
Although colon cancer has a genetic basis, a new study shows that the ever-changing microbial composition of the gut may play a role in who ultimately develops cancer.
Published in The Journal of Experimental Medicine, the study found that relatively minor changes to the microbiome of the intestines can influence the development of serrated polyps, benign tumors that can become malignant.
The observations came from a line of transgenic mice that overexpress the growth factor HB-EGF throughout the intestines, but they developed polyps in only one area. “We wanted to know why the polyps developed only in the cecum,” says senior author Sergio Lira, MD, PhD, director of the Immunology Institute at the Icahn Institute of Medicine at Mt. Sinai in New York, NY.
The serrated polyps in these mice were found to have elevated expression of antimicrobial genes; to determine whether this played a role in serrated polyp pathogenesis, half of the mice were treated with a broad-spectrum antibiotic cocktail. “The results were striking,” says Lira. “There were no polyps in the mice treated with antibiotics.”
Investigators then looked at the impact of antibiotics on the progression of established tumors. “Again, we were surprised,” says Lira. “The antibiotics reduced the size of established polyps in the treated mice, which suggests that the bacteria not only were important for tumor formation, but also played a role in the continued growth of the lesions.”
To promote adoption of a different microbiota and exclude non-specific effects of the broad-spectrum antibiotic, the team performed embryo transfer and found a significant reduction in the development of polyps in the transplanted mice. “The transplanted mice acquired a different microbiome from the adoptive mothers after birth,” notes Lira.
Comparing the data, the investigators found that most of the bacteria in the polyps belonged to the Clostridiales family. The team then treated the transgenic mice with vancomycin, which targets gram-positive bacteria including Clostridiales. In the vancomycin-treated mice, polyp incidence and size was significantly reduced, suggesting that members of the Clostridiales family are involved in the formation of the polyps. “It is unclear at this point if one or more members of the family are required,” says Lira.
During the study, investigators noticed upregulation of inflammatory molecules within the polyps compared to the surrounding area. “The interplay between genetic mutations, microbes, and inflammation is important for polyp development,” adds Lira.
Additional research, including longitudinal studies, is required to shed light on the impact of gut bacteria in human cancers. “One of the things we'd like to know is whether people with these types of tumors benefit from targeted antibiotic treatment,” says Lira.
At this point, he cautions against large-scale alterations in gut bacteria. “Attempts to manipulate the microbiome are still in their infancy,” he notes. “We need to have a better understanding of what groups of bacteria are doing, and how best to confer protection without causing harm.”
