Severe Cognitive Decline in Long-term Care Is Related to Gut Microbiome Production of Metabolites Involved in Neurotransmission, Immunomodulation, and Autophagy

Aging-associated cognitive decline affects more than half of those in long-term residential aged care. Emerging evidence suggests that gut microbiome-host interactions influence the effects of modifiable risk factors. We investigated the relationship between gut microbiome characteristics and severity of cognitive impairment (CI) in 159 residents of long-term aged care. Severe CI was associated with a significantly increased abundance of proinflammatory bacterial species, including Methanobrevibacter smithii and Alistipes finegoldii, and decreased relative abundance of beneficial bacterial clades. Severe CI was associated with increased microbial capacity for methanogenesis, and reduced capacity for synthesis of short-chain fatty acids, neurotransmitters glutamate and gamma-aminobutyric acid, and amino acids required for neuroprotective lysosomal activity. These relationships were independent of age, sex, antibiotic exposure, and diet. Our findings implicate multiple gut microbiome-brain pathways in aging-associated cognitive decline, including inflammation, neurotransmission, and autophagy, and highlight the potential to predict and prevent cognitive decline through microbiome-targeted strategies.