Abstract

Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. We aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. We included 1430 participants from a prospective cohort study with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. The validation analyses were conducted in an Alzheimer’s disease case-control study (replication study 1, n=90) and another community-based cohort (replication study 2, n=1300) with cross-sectional dataset. Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development.

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