Jennifer A. Wargo, MD, MMSC
In the early 20th century, research findings about the nature of microbes upended the traditional understanding of science and medicine. The acceptance of germ theory revolutionized medical care, and ultimately led to improved public health and longer life spans. A similar microbe-driven revolution may be afoot in oncology, as researchers uncover and untangle the relationships between the microbiome and cancer.
Between 2005 and 2015, the number of articles published about the microbiome and cancer increased by nearly 2000%.1
Researchers have found relationships between the oral microbiome and esophageal cancer; between the vaginal and uterine microbiomes and endometrial cancer; and between the gut microbiome and the efficacy of checkpoint inhibitors. And, although the research is young, the results so far suggest that the microbiome may, at least in part, help answer 2 of oncology’s most persistent questions: What causes cancer? Why do some people respond favorably to cancer treatment whereas others do not?
The microbiome is broadly defined as the “collective genomes of the microbes, composed of bacteria, bacteriophage, fungi, protozoa, and viruses, that live inside and on the human body.”2
Altogether, these bacteria and microorganisms are characterized as the microbiota, an “ensemble” that inhabits the epithelial barrier surfaces of the human body and influences a range of physiological functions, including metabolism and immunity.3
Researchers from the University of North Carolina at Chapel Hill describe interactions between the microbiota and bodily systems within the context of the “Hallmarks of Cancer” that Douglas Hanahan, PhD, and Robert A. Weinberg, PhD, have elucidated (FIGURE).4
Fulbright and colleagues maintain that these interactions are so complex that the focus should be on the microbial metabolome, the collection of low-molecular-weight molecules in the cell, rather than on individual metabolites.4
Figure. How Microbial Signals Modulate Hallmarks of Cancer
Two decades ago, it was nearly impossible to systematically study the human microbiome because most human bacteria cannot grow outside of the human body. Research initiatives such as the Human Microbiome Project, which the National Institutes of Health launched in 2007 as an extension of the Human Genome Project,2
have helped expand knowledge about the microbiota. Advances in genomic sequencing also have brought the microbiome into reach, scientifically speaking. Now, researchers can sequence the DNA of cells and identify the bacterial profile based on DNA formation. As a result, researchers have identified distinct microbiomes of different organs within the body, as well as differences between the microbiomes of individuals.
Role in Cancer
Ninety-nine percent of the microbial mass in the human body is found within the gastrointestinal (GI) tract,5
but the microbiota exerts systemic as well as local effects on physiological functions. In terms of carcinogenesis, the GI microbiota has been linked to cancers in the GI tract and in other organs (TABLE).3
Although GI activity of these microorganisms has been extensively studied, understanding is also growing about the microbiota in other epithelial barriers, such as the mouth and skin.3
Table. Cancers Linked to GI Microbiota
Scientists and physicians, for instance, have long been aware of a link between poor oral health and cancer. “We know that periodontal disease mysteriously is related to increased risk of upper gastrointestinal cancer,” said Jiyoung Ahn, PhD, an associate professor of Population Health and Environmental Medicine at NYU School of Medicine, and the associate director of Population Science at NYU Perlmutter Cancer Center in New York City. “But people didn’t have a good explanation why. Some people didn’t believe it at all.”
Research into the microbiome reveals that the same bacteria responsible for poor oral health may also be related to the development of cancer. A 2016 study published in Gut found that the presence and concentration of particular types of oral bacteria may increase or decrease the risk of developing cancers of the upper GI tract.6