Aging is an inexorable, universal process affecting every organ system in which organisms lose fitness and the ability to maintain homeostasis. One of the main consequences of aging across species is a decline in neurological and cognitive function. This is in part due to age-associated neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, but also happens independent of these pathological processes in age-associated cognitive decline. Recently, accumulating evidence points to the influence of factors outside of the brain that affect cognitive aging. One of these contributors is the gut microbiome – the collection of trillions of microorganisms that inhabit our gastrointestinal tract. In recent years, studies in mice and rats have shown that the microbiome from older animals is able to impair cognition when transplanted into young animals. Using a combination of animal behavior, sequencing, genetic manipulations, and pharmacological interventions, I show that the aged microbiome impairs cognition in mice in a dominant negative manner; I identify a particular species, Parabacteroides goldsteinii, that is increased in prevalence in the aged mouse microbiome and is sufficient to impair cognition. Using untargeted metabolomics, I then found a class of metabolites produced by P. goldsteinii, medium-chain fatty acids (MCFAs), that impair cognition through GPR84 signaling on myeloid cells. This immune cell signaling results in production of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF) and interleukin 1 beta (IL-1), that impair the function of the vagus nerve. I also show that cognitive impairment is a generalizable feature of peripheral inflammation, such that other forms of peripheral inflammation, like colitis, cancer, or infection, also impair memory in a vagus-nerve-dependent manner. Together, these findings elucidate a novel mechanism contributing to age-associated cognitive decline and identify new targets for therapeutic intervention in aging, inflammatory bowel disease, and cancer that affect hundreds of millions of people.