Intestinal microbiota may be linked to diet and the incidence of colorectal cancer

A diet rich in whole grain and dietary fiber—a prudent diet—may be associated with a lower risk for colorectal cancers positive for the presence of Fusobacterium nucleatum, but not those that are F. nucleatum-negative, according to researchers at the Dana-Farber Cancer Institute and Massachusetts General Hospital, Boston, MA. These results provide some of the strongest evidence to date of the potential role of intestinal microbiota in mediating colorectal neoplasms, and are published online in JAMA Oncology.

“Though our research dealt with only one type of bacteria, it points to a much broader phenomenon – that intestinal bacteria can act in concert with diet to reduce or increase the risk of certain types of colorectal cancer,” said Shuji Ogino, MD, PhD, of Dana-Farber, Harvard T.H. Chan School of Public Health, and Brigham and Women’s Hospital, Boston, MA, the co-senior author of the study with Charles Fuchs, MD, MPH, director of the Gastrointestinal Cancer Center, Dana-Farber and Brigham and Women’s, and Andrew Chan, MD, MPH, of Massachusetts General Hospital, Brigham and Women’s, and the Broad Institute of MIT and Harvard.

“These data are among the first in humans that show a connection between long-term dietary intake and the bacteria in tumor tissue. This supports earlier studies that show some gut bacteria can directly cause the development of cancers in animals,” added Dr. Chan.

Previous studies paved the way for their research.

“Recent experiments have suggested that F. nucleatum may contribute to the development of colorectal cancer by interfering with the immune system and activating growth pathways in colon cells,” Dr. Ogino said.

“One study showed that F. nucleatum in the stool increased markedly after participants switched from a prudent to a Western-style, low-fiber diet. We theorized that the link between a prudent diet and reduced colorectal cancer risk would be more evident for tumors enriched with F.nucleatum than for those without it," he added.

For this study, Drs. Ogino, Fuchs, Chan, and colleagues collected dietary records from 137,217 subjects who participated in the Nurses’ Health Study and the Health Professionals Follow-up Study. In these subjects, 1,019 incident colon and rectal cancer cases occurred, from which researchers assessed tumor samples for the presence of F. nucleatum via quantitative polymerase chain reaction.

F. nucleatum data were documented over 26 to 32 years of follow-up, for a total of 3,643,562 person-years. These data were then combined with dietary information and the incidence of cancer.

Researchers found that the association between a prudent diet with colorectal cancer differed significantly according to tissue F. nucleatum status (P=0.01 for heterogeneity), and prudent diet score was associated with a lower risk of F. nucleatum-positive cancers (P=0.003 for trend; multivariable HR: 0.43; 95% CI: 0.25-0.72 for highest vs lowest prudent score quartile). They found no association, however, with F. nucleatum-negative cancers (P=0.47 for trend, multivariable HR: 0.95, 95% CI: 0.77-1.17). No significant heterogeneity between subgroups related to Western dietary pattern scores was evident.

“Our findings offer compelling evidence of the ability of diet to influence the risk of developing certain types of colorectal cancer by affecting the bacteria within the digestive tract," Dr. Ogino concluded.

Dr. Chan added: “The results of this study underscore the need for additional studies that explore the complex interrelationship between what someone eats, the microorganisms in their gut, and the development of cancer.”

This work was supported by US National Institutes of Health (grants P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA137178, K24 DK098311, R01 CA202704, R01 CA151993, R35 CA197735, and K07 CA190673); and by grants from The Project P Fund for Colorectal Cancer Research, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance.