Gut microbial signatures associated with cognitive performance in older adults from the long-lived Okinawan population

Abstract Recent cross-sectional studies have reported associations between gut microbiota and cognitive function in older adults. However, this relationship has not been explored in Okinawa, Japan, a region historically recognized for exceptional human longevity. In this cross-sectional study, we recruited 155 community-dwelling adults aged 65 or older from Okinawa Prefecture, Japan. Participants underwent comprehensive neuropsychological assessments and were classified as cognitively normal, having mild cognitive impairment (MCI), or having dementia, based on Montreal Cognitive Assessment-Japanese version (MoCA-J) and Clinical Dementia Rating (CDR) scores. We analyzed their gut microbiota using 16S rRNA gene amplicon and whole-genome shotgun sequencing. We found that both gut microbial alpha diversity and community structure were significantly associated with cognitive status and performance scores. Species-level analysis revealed that Fusicatenibacter saccharivorans , an anti-inflammatory bacterium, was positively correlated with the cognitive performance score and co-occurred with Faecalibacterium prausnitzii , a species that ameliorates cognitive impairment in an Alzheimer’s disease mouse model. Conversely, the mucin degradation pathway, indicative of mucosal barrier dysfunction, was enriched in the MCI group. In summary, our findings provide insight into microbial and functional signatures associated with cognitive performance in older adults. Further longitudinal studies, replication studies in independent cohorts, and experimental validation are needed to confirm these findings.