Gut microbiota mediates the association between aging and cognitive function: evidence from a population-based Kyotango study linking diet, Bifidobacterium, and Mini-Mental State Examination (MMSE) score

Objective Age-related cognitive decline is a major public health concern; however, the biological pathways linking aging to cognitive function remain poorly understood. Emerging evidence suggests that gut microbiota may influence brain health; however, human studies integrating clinical factors, diet, microbiota, and cognition remain limited. Design We conducted a cross-sectional analysis of community-dwelling older adults (N = 578). Clinical variables, blood biomarkers, and dietary intake were assessed using a validated questionnaire, and gut microbiota profiles (based on 16S rRNA sequencing) were analyzed in relation to cognitive function measured using the Mini-Mental State Examination (MMSE). Multivariable regression models were used to identify independent determinants of MMSE. Mediation analysis was performed to evaluate whether the gut microbiota mediated the association between age and cognitive function. Additional analyses were conducted in a subset excluding participants with suspected dementia (MMSE ≤ 23) to examine diet–microbiota relationships (n = 535). Results In multivariable analysis, age, frailty, renal function, inflammatory markers, and specific gut microbial taxa were independently associated with MMSE. Among the microbial features, Bifidobacterium showed a significant positive association with cognitive function. Age was inversely associated with Bifidobacterium , whereas Bifidobacterium was positively associated with MMSE. Mediation analysis demonstrated that Bifidobacterium partially mediated the association between age and MMSE (indirect effect: −0.0107, 95% CI: −0.0196 to − 0.0034, p = 0.004). Furthermore, dietary analysis revealed that milk intake was positively associated with Bifidobacterium , suggesting a modifiable pathway linking diet, microbiota, and cognition. Conclusions Our findings provide evidence that age-related changes in the gut microbiota, particularly reductions in Bifidobacterium , partially mediate cognitive decline in older adults. These results support the existence of a diet–microbiota–brain axis and highlight the gut microbiota as a potential target for interventions aimed at preserving cognitive function during aging. Trial registration number The UMIN Clinical Trials Registry (UMIN-CTR), UMIN000019486, and UMIN0000 000061232 were registered on December 1, 2015, and April 11, 2026, respectively.