Arizona State University mouse study finds high-fat diet leaves 18% of DNA changes in intestinal stem cells

Researchers at Arizona State University, led by Miyeko Mana, fed mice a Western-style high-fat diet for about six months and found that the diet increased intestinal stem cell numbers and growth speed compared with low-fat diet controls. In mice genetically predisposed to intestinal cancer, the high-fat diet also produced more and larger tumors. The team reported in Stem Cell Reports that some DNA regulatory changes in the stem cells persisted after the mice switched back to a low-fat diet, with about 18% remaining after four weeks.

The study used mouse models rather than human participants, so the findings describe biology in an experimental system. Researchers compared mice on high-fat and low-fat diets, then measured intestinal stem cell behavior and tumor burden in cancer-prone animals. They also examined DNA-level changes, described as chromatin states, which are chemical and structural marks that influence how genes are read. After repeated high-fat diet exposure, stem cells responded more quickly and strongly, and cancer-prone mice developed more and larger tumors than after a single exposure period. The article summary did not provide funding details.

The work adds a mechanistic layer to a broad public health pattern: obesity is associated with a 30% to 50% higher risk of colon cancer, and about one in 25 people develop the disease in their lifetime. Prior studies have linked high-fat diets to inflammation, metabolism and tumor growth. This study focuses on intestinal stem cells, the cells that renew the gut lining, and suggests that diet can leave a molecular memory that makes those cells more responsive to later high-fat exposure.

For people at risk of colon cancer, the finding points to a possible biological pathway connecting diet, stem cell regulation and tumor development, though it does not show that a low-fat diet prevents cancer in humans. The study design can show association and causation in mice under controlled conditions; it cannot prove the same mechanism in people. A stronger human evidence base would require studies that measure comparable intestinal chromatin changes, diet exposure and cancer outcomes.