High fat diet and stem cells: Linking diet to intestinal tumor formation.

In recent years, diet has been increasingly recognized as a significant modifiable risk factor for cancer initiation and progression in multiple organ systems1. The pathophysiological effects of diet have garnered attention among the scientific community in response to the increasing worldwide adoption of the Western diet and accompanying rise in obesity rates. Indeed, epidemiological studies have shown that obesity is associated with elevated risk of many types of cancer, particularly those of the gastrointestinal tract 2. A main driver in how diet contributes to cancer incidence is by changing the biology of long-lived adult stem cells. Such adult stem cells balance self-renewal divisions (divisions that generate stem cells) and differentiation divisions (divisions that generate non-stem cell progenitors) in response to multiple environmental inputs like diet to maintain tissue homeostasis. Moreover, adult stem cells in many tissues have been implicated as the cells that accumulate the initial mutations that ultimately beget cancers1,3. This paradigm has been best illustrated in the intestine, where Lgr5+ intestinal stem cells (ISCs) initiate and serve as the cells-of-origin for colorectal cancer4. Although pro-obesity diets and obesity predispose to intestinal cancers, how they alter the biology and vulnerability of intestinal stem and progenitor cells to form tumors is uncertain.