Healthful plant-based diet, gut enterotype, and cognition in a rural Chinese elderly cohort: A longitudinal multi-omics study

The gut microbiome may shape how diet influences cognitive aging, but population-based evidence remains limited. In 784 older adults living in rural China (70-98 years old) with fecal metagenomics and structured dietary assessment, a modified healthful plant-based diet index (mHPDI) is associated with distinct gut microbial structure and taxonomic shifts (15 species, 17 genera). Among participants with repeated cognitive measurements, higher mHPDI is associated with better global cognition, with stronger benefits in participants with non-Prevotella-dominant enterotypes (highest versus lowest tertile β = 0.34, 95% confidence interval [CI], 0.16 to 0.52) than in those with a Prevotella-dominant enterotype (0.04, -0.22 to 0.29; p interaction = 0.04). Enterotype-associated differences in microbial metabolic pathways, including preQ0 and L-isoleucine biosynthesis, parallel this heterogeneity. Moreover, 12 circulating microbiota-related metabolites (primarily amino acids and short-chain fatty acids) are linked to mHPDI. A composite score comprising these metabolites mediates 11.0% of the mHPDI-cognition association (p mediation = 0.02), with branched-chain amino acids as major contributors. These findings suggest that gut microbial context may shape diet-cognition associations.