How Lactoferrin Helps Heal Gut Damage

Lactoferrin, a protein found in milk, has been shown to help protect the gut from damage caused by a toxin called deoxynivalenol (DON). Researchers wanted to understand how lactoferrin works at a genetic level to reduce inflammation and oxidative stress in the gut. When mice were fed a diet contaminated with DON, their gut lining showed signs of damage. The villi, which are tiny finger-like projections that help absorb nutrients, became shorter and wider. The crypts, which are small pits that house stem cells, became deeper. This damage was accompanied by an increase in harmful reactive oxygen species (ROS) and a decrease in antioxidants like superoxide dismutase (SOD) and catalase (CAT). The mice also had lower levels of energy-producing molecules like ATP. However, when lactoferrin was added to the diet, it helped reverse these effects. The gut lining looked healthier, and the levels of harmful molecules decreased while the levels of protective molecules increased. To understand how lactoferrin works, researchers looked at the genes that were turned on or off in the gut cells. They found that DON exposure turned down genes involved in cell growth and turned up genes involved in inflammation and oxidative stress. Lactoferrin helped reverse these changes, turning down inflammation and oxidative stress genes and turning up cell growth genes. The researchers also found that lactoferrin affects how genes are regulated by tiny chemical tags attached to the DNA. These tags, called histone modifications, can turn genes on or off. Lactoferrin increased the loss of these tags on certain genes, suggesting that it helps regulate gene activity. One gene that seemed to be particularly important was NR5A2. This gene helps regulate other genes involved in oxidative stress. Lactoferrin helped increase the activity of NR5A2, which in turn helped regulate the activity of other genes like Ncoa4 and Prdx3. In summary, lactoferrin helps protect the gut from damage caused by DON by regulating gene activity through histone modifications. This helps reduce inflammation and oxidative stress, promoting gut health.