Microbial Link Between Western-Style Diet and Incidence of Colorectal Cancer Uncovered

Shuji Ogino

New research builds the case that a Western-style diet — rich in red and processed meat, sugar and refined grains/carbohydrates — is tied to higher risk of colorectal cancer through the intestinal microbiota. Investigators from Brigham and Women’s Hospital with collaborators looked at data from more than 134,000 participants from two U.S.-wide prospective cohort studies. The team analyzed dietary patterns as well as DNA from Escherichia coli strains found in more than 1,000 colorectal tumors. The team looked for bacterial strains carrying a distinct genetic island known as polyketide synthase (pks). Pks encodes an enzyme that has been shown to cause mutations in human cells. Overall, the team found that Western diet was associated with colorectal tumors containing high amounts of pks+ E. coli but not with tumors containing little to no amount of pks+ E. coli.

“These findings support our hypothesis that Western-style diets increase colorectal cancer risk through its effect on pks+ E. coli,” said corresponding author Shuji Ogino, MD, PhD, MS, of the Program in Molecular Pathological Epidemiology in the Department of Pathology at the Brigham. “This is the first study to link Western diet with specific pathogenic bacteria in cancer.  Our next question is which component of western-style diet and lifestyle relates to colorectal cancer containing this bacterial species.”

Read more in Gastroenterology.

Study Uncovers Pancreas Cell Type-Specific Activities of IL18

Guo-Ping Shi

Both type 1 and type 2 diabetes are characterized by the loss of β cells and insulin secretion. Regenerating β cells from other cell types, such as α cells, has been proposed as a potential therapeutic strategy for diabetes. Inflammation is thought to be connected to diabetes progression, but many questions remain about the role of specific markers of inflammation, such as interleukin 18 (IL18) in the disease and in specific cell types. In a new study, researchers have found that in human and mouse pancreases, α cells express IL18, acinar cells express traditional IL18 receptors, and β cells express an alternative IL18 receptor known as the Na-Cl co-transporter (NCC). The team’s findings suggest that IL18, together with the glucagon-like peptide-1 (GLP1) from α cells, uses NCC and GLP1 receptor on β cells for β-cell development, insulin secretion, and insulin signaling. Like GLP1 agonists, IL18 may have therapeutic potential for patients with obesity and diabetes. Yet, interruption of IL18 interactions with its receptors has been shown to be effective at reducing atherosclerosis in experimental models. Therefore, targeting IL18 in patients with cardiovascular disease may damage β-cell functions.

“These findings provide insights into the role of IL18 signaling in regulating islet β cell proliferation and may help guide future efforts to protect these IL18 pathways as a potential strategy to expand β cells and increase islet mass in diabetes,” said senior author Guo-Ping Shi, ScD, a principal investigator in the Brigham’s Division of Cardiovascular Medicine.

Read more in Developmental Cell.