O type blood is the ‘universal donor’ type as it can be transfused into nearly all patients with any blood type, but it is often in short supply. Now, Rahfeld et al. report an enzymatic pathway in the human gut microbiome that converts A type blood into the universal donor type, which could lead to an increase in the supply of universal donor blood. ABO blood grouping is determined by antigens on the surface of red blood cells (RBCs). The antigens are carbohydrate structures with terminal sugars, but O type RBCs lack these sugars. The authors performed a functional metagenomic screen of the human gut microbiome for enzymes that remove A and B type sugar antigens from RBCs and found an enzyme pair encoded in the genome of the obligate anaerobe Flavonifractor plautii (a N-acetylgalactosamine deacetylase and a galactosaminidase) that together efficiently convert the A antigen to the H antigen of O type blood.