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The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3–4 months) or old (19–20 months) donor mice into aged recipient mice (19–20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging. The gut microbiome can change with age and influence aging-related diseases systemically, including in the brain. The authors show that rejuvenation of the gut microbiome by fecal microbiota transplantation from young mice reverses aging-induced deficits in the hippocampal immune system, metabolome and transcriptome, and rescues selective cognitive deficits.