Aging is associated with increased microbial compounds in blood because of increased permeability of the intestinal barrier. Increased levels of microbial compounds in blood stimulate the activation of the IL-1 axis in BM, which drives the HSC myeloid differentiation skewing. The effect on HSCs is IL-1 receptor-dependent and it can be targeted by administration of IL-1 inhibitors or by antibiotic treatment. This gut–BM axis reinforces the importance of the intestinal integrity and the microbiota in allo-HSCT and also as a possible therapeutic target for the aging-related HSC myeloid skewing. Graphics were modified from Servier Medical Art, licensed under a Creative Common Attribution 3.0 Generic License. http://smart.servier.com/.