Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum
Abstract Background Gut microbiota dysbiosis is linked to Alzheimer’s disease (AD), but our understanding of the molecular and neuropathological bases underlying such association remains fragmentary. Methods Using 16S rDNA amplicon sequencing, untargeted metabolomics, and multi-modal magnetic resona...
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BMC
2025-02-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-025-01683-0 |
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| author | Han Zhao Xia Zhou Yu Song Wenming Zhao Zhongwu Sun Jiajia Zhu Yongqiang Yu |
| author_facet | Han Zhao Xia Zhou Yu Song Wenming Zhao Zhongwu Sun Jiajia Zhu Yongqiang Yu |
| author_sort | Han Zhao |
| collection | DOAJ |
| description | Abstract Background Gut microbiota dysbiosis is linked to Alzheimer’s disease (AD), but our understanding of the molecular and neuropathological bases underlying such association remains fragmentary. Methods Using 16S rDNA amplicon sequencing, untargeted metabolomics, and multi-modal magnetic resonance imaging, we examined group differences in gut microbiome, fecal metabolome, neuroimaging measures, and cognitive variables across 30 patients with AD, 75 individuals with mild cognitive impairment (MCI), and 61 healthy controls (HC). Furthermore, we assessed the associations between these multi-omics changes using correlation and mediation analyses. Results There were significant group differences in gut microbial composition, which were driven by 8 microbial taxa (e.g., Staphylococcus and Bacillus) exhibiting a progressive increase in relative abundance from HC to MCI to AD, and 2 taxa (e.g., Anaerostipes) showing a gradual decrease. 26 fecal metabolites (e.g., Arachidonic, Adrenic, and Lithocholic acids) exhibited a progressive increase from HC to MCI to AD. We also observed progressive gray matter atrophy in broadly distributed gray matter regions and gradual micro-structural integrity damage in widespread white matter tracts along the AD continuum. Integration of these multi-omics changes revealed significant associations between microbiota, metabolites, neuroimaging, and cognition. More importantly, we identified two potential mediation pathways: (1) microbiota → metabolites → neuroimaging → cognition, and (2) microbiota → metabolites → cognition. Conclusion Aside from elucidating the underlying mechanism whereby gut microbiota dysbiosis is linked to AD, our findings may contribute to groundwork for future interventions targeting the microbiota-metabolites-brain-cognition pathways as a therapeutic strategy in the AD continuum. |
| format | Article |
| id | doaj-art-4ce8d33c7307420e9b671e46c97d2288 |
| institution | Kabale University |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-4ce8d33c7307420e9b671e46c97d22882025-02-02T12:11:57ZengBMCAlzheimer’s Research & Therapy1758-91932025-02-0117111510.1186/s13195-025-01683-0Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuumHan Zhao0Xia Zhou1Yu Song2Wenming Zhao3Zhongwu Sun4Jiajia Zhu5Yongqiang Yu6Department of Radiology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Radiology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Radiology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Radiology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Radiology, The First Affiliated Hospital of Anhui Medical UniversityAbstract Background Gut microbiota dysbiosis is linked to Alzheimer’s disease (AD), but our understanding of the molecular and neuropathological bases underlying such association remains fragmentary. Methods Using 16S rDNA amplicon sequencing, untargeted metabolomics, and multi-modal magnetic resonance imaging, we examined group differences in gut microbiome, fecal metabolome, neuroimaging measures, and cognitive variables across 30 patients with AD, 75 individuals with mild cognitive impairment (MCI), and 61 healthy controls (HC). Furthermore, we assessed the associations between these multi-omics changes using correlation and mediation analyses. Results There were significant group differences in gut microbial composition, which were driven by 8 microbial taxa (e.g., Staphylococcus and Bacillus) exhibiting a progressive increase in relative abundance from HC to MCI to AD, and 2 taxa (e.g., Anaerostipes) showing a gradual decrease. 26 fecal metabolites (e.g., Arachidonic, Adrenic, and Lithocholic acids) exhibited a progressive increase from HC to MCI to AD. We also observed progressive gray matter atrophy in broadly distributed gray matter regions and gradual micro-structural integrity damage in widespread white matter tracts along the AD continuum. Integration of these multi-omics changes revealed significant associations between microbiota, metabolites, neuroimaging, and cognition. More importantly, we identified two potential mediation pathways: (1) microbiota → metabolites → neuroimaging → cognition, and (2) microbiota → metabolites → cognition. Conclusion Aside from elucidating the underlying mechanism whereby gut microbiota dysbiosis is linked to AD, our findings may contribute to groundwork for future interventions targeting the microbiota-metabolites-brain-cognition pathways as a therapeutic strategy in the AD continuum.https://doi.org/10.1186/s13195-025-01683-0Alzheimer’s diseaseGut microbiomeFecal metabolomeNeuroimagingCognition |
| spellingShingle | Han Zhao Xia Zhou Yu Song Wenming Zhao Zhongwu Sun Jiajia Zhu Yongqiang Yu Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum Alzheimer’s Research & Therapy Alzheimer’s disease Gut microbiome Fecal metabolome Neuroimaging Cognition |
| title | Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum |
| title_full | Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum |
| title_fullStr | Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum |
| title_full_unstemmed | Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum |
| title_short | Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum |
| title_sort | multi omics analyses identify gut microbiota fecal metabolites brain cognition pathways in the alzheimer s disease continuum |
| topic | Alzheimer’s disease Gut microbiome Fecal metabolome Neuroimaging Cognition |
| url | https://doi.org/10.1186/s13195-025-01683-0 |
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