Aging-related dysbiosis is associated with increased intestinal permeability and systemic overproduction of proinflammatory cytokines that drive numerous “inflamm-aging” phenotypes. In the hematopoietic system, this includes myeloid-restricted lineage activity, with concomitant reductions in lymphocyte production, as well as a reduction in long-term HSC repopulating activity. Zeng et al show that transplantation of young fecal microbiota into aged mice leads to an increased proportion of Lachnospiraceae bacteria present in the intestine, which associates with increased production of tryptophan- and indole-associated metabolites. These are sufficient to reduce gut permeability and systemic inflammation, in turn rejuvenating HSC function and production of B lymphocytes in the bone marrow. Figure generated using BioRender.