Gut microbiome signatures predict cognitive impairment in older cancer survivors

Cancer treatments are improving, and the population of cancer survivors is steadily increasing. However, many survivors experience long-term side effects, including chemobrain and other age-related geriatric disorders like cognitive impairment (CI), severely impacting their quality of life. Emerging studies suggest that the gut microbiome plays a central role in cognitive health. However, the long-term effects of cancer treatments on the microbiome, and how these changes impact cognitive health in survivors, remain largely unknown. Shotgun metagenomic data from 150 older adults (≥ 60 years old, including 49 cancer survivors and 101 controls) from the Microbiome in Aging Gut and Brain (MiaGB) consortium revealed that Tyzzerella, Eggerthella lenta, and Bacteroides vulgatus were specific markers of the cancer survivor gut and could differentiate cancer survivorship in this cohort. Microbiome signatures were distinct in cancer survivors with CI compared to those without and differed from those seen in non-cancer individuals with CI. Bacterial taxa including Streptococcus thermophilus and Firmicutes bacterium CAG 114 were significantly reduced in cancer survivors and strongly associated with CI. Importantly, metabolic pathway analysis revealed that microbial neurotransmitter synthesis was significantly depleted in the gut of cancer survivors, suggesting a mechanistic link to CI. Our results suggest that microbiome signatures predict cancer survivorship and the risk of CI in older adults, potentially by depleting neurotransmitter synthesis in the gut. These findings aid in establishing the role of the microbiome in predicting cancer survivorship and CI risk, which is valuable in the development of novel therapies to support the growing population of cancer survivors.