Dietary miR-451 protects erythroid cells from oxidative stress via increasing the activity of Foxo3 pathway

One fundamental issue in public health is the safety of food products derived from plants and animals. A recent study raised a concern that microRNAs, which widely exist in everyday foods, may alter consumers’ functions. However, some studies have strongly questioned the likelihood of dietary uptake of functional microRNAs in mammals. Here we use a microRNA gene knockout animal model to show that miR-144/451 null mice can orally uptake miR-451 from a daily chow diet, and ingestion of wild type blood, that contains abundant miR-451, also enhances the level of miR-451 in the circulating blood of knockout mice. Moreover, reducing miR-451 level in miR-144/451 knockout blood by consuming food lacking miR-451 reduces the anti-oxidant capacity of miR-144/451 null red blood cells by targeting the 14-3-3ζ/Foxo3 pathway, while increasing miR-451 level via gavage-feeding of wild type blood increases the anti-oxidant capacity of miR-144/451 null red blood cells. We conclude that 1) some miRNAs in food can pass through the gastrointestinal tract into the blood to affect consumers’ function and 2) microRNA knockout animals such as miR-144/451 null mice can acquire the deleted genetic information from daily foods, which might alter the results and conclusions from the studies using such animals.