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. 2025 Feb 27;17(1):52.
doi: 10.1186/s13195-025-01697-8.

Brain age mediates gut microbiome dysbiosis-related cognition in older adults

Sang Joon Son #  1 , Dong Yun Lee #  2 , Hyun Woong Roh  1 , Maria Ly  3   4 , Antonija Kolobaric  5 , Howard Aizenstein  6   7 , Carmen Andreescu  6 , Eldin Jašarević  8   9   10 , Tharick A Pascoal  6 , Pamela C L Ferreira  6 , Bruna Bellaver  6 , Yong Hyuk Cho  1 , Sunhwa Hong  1 , You Jin Nam  1 , Bumhee Park  2   11 , Narae Kim  2   12 , Jin Wook Choi  13 , Jae Youn Cheong  14   15 , Yoon-Keun Kim  16 , Tae-Seop Shin  16 , Chil-Sung Kang  16 , Cheol-O Kwon  16 , Seo-Yoon Yoon  16 , Chang Hyung Hong  17 , Helmet T Karim  18   19
Affiliations

Brain age mediates gut microbiome dysbiosis-related cognition in older adults

Sang Joon Son et al. Alzheimers Res Ther. .

Abstract

Background: Recent studies have focused on improving our understanding of gut microbiome dysbiosis and its impact on cognitive function. However, the relationship between gut microbiome composition, accelerated brain atrophy, and cognitive function has not yet been fully explored.

Methods: We recruited 292 participants from South Korean memory clinics to undergo brain magnetic resonance imaging, clinical assessments, and collected stool samples. We employed a pretrained brain age model- a measure associated with neurodegeneration. Using cluster analysis, we categorized individuals based on their microbiome profiles and examined the correlations with brain age, Mental State Examination (MMSE) scores, and the Clinical Dementia Rating Sum of Box (CDR-SB).

Results: Two clusters were identified in the microbiota at the phylum level that showed significant differences on a few microbiotas phylum. Greater gut microbiome dysbiosis was associated with worse cognitive function including MMSE and CDR-SB; this effect was partially mediated by greater brain age even when accounting for chronological age, sex, and education.

Conclusions: Our findings indicate that brain age mediates the link between gut microbiome dysbiosis and cognitive performance. These insights suggest potential interventions targeting the gut microbiome to alleviate age-related cognitive decline.

Keywords: Brain age; Cognition; Gut microbiome.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: BICWALZS was registered in the Korean National Clinical Trial Registry (KCT0003391|| Registration Date: 2018/07/04|| http://cris.nih.go.kr/cris/en/use_guide/cris_introduce.jsp ). The research protocol was approved by the Institutional Review Boards of Ajou University Hospital (AJOUIRB-SUR-2021-038) and conducted in accordance with the current version of the Declaration of Helsinki. Written informed consent was obtained from all the participants and caregivers. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Dirichlet multinomial mixtures (DMM) clustering using microbiome data Comparison of major gut microbiota at the phylum level between Group 1 and Group 2. The boxplot represents the relative abundance (%) of six prominent phyla, including Firmicutes, Actinobacteriota, Proteobacteria, Bacteroidota and Verrucomicrobiota. Group 1 is shown in blue, and Group 2 is shown in red. Asterisks indicate statistically significant differences in relative abundance between the two groups (p < 0.05)
Fig. 2
Fig. 2
Mediation analysis among cluster group, brain age, and cognitive function measures Mediation analysis adjusted for sex, age, and education. Abbreviations: CDR-SB, Clinical Dementia Rating Sum of Box; MMSE, Mini-Mental State Examination; * p < 0.05; **p < 0.01
See this image and copyright information in PMC

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