Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathology
Abstract Background Emerging evidence highlights the bidirectional communication between the gut microbiota and the brain, suggesting a potential role for gut dysbiosis in Alzheimer’s disease (AD) pathology and cognitive decline. Existing literature on gut microbiota lacks species-level insights. Th...
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| Format: | Article |
| Language: | English |
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BMC
2025-05-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-025-01769-9 |
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| author | Kang-Chen Fan Chen-Ching Lin Yen-Ling Chiu Seong-Ho Koh Yi-Chien Liu Yi-Fang Chuang |
| author_facet | Kang-Chen Fan Chen-Ching Lin Yen-Ling Chiu Seong-Ho Koh Yi-Chien Liu Yi-Fang Chuang |
| author_sort | Kang-Chen Fan |
| collection | DOAJ |
| description | Abstract Background Emerging evidence highlights the bidirectional communication between the gut microbiota and the brain, suggesting a potential role for gut dysbiosis in Alzheimer’s disease (AD) pathology and cognitive decline. Existing literature on gut microbiota lacks species-level insights. This study investigates gut microbiota alterations in mild cognitive impairment (MCI), focusing on their association with comprehensive AD biomarkers, including amyloid burden, tau pathology, neurodegeneration, and cognitive performance. Methods We analyzed fecal samples from 119 individuals with MCI and 320 cognitively normal controls enrolled in the Taiwan Precision Medicine Initiative on Cognitive Impairment and Dementia cohort. Shotgun metagenomic sequencing was conducted with taxonomic profiling using MetaPhlAn4. Amyloid burden and plasma pTau181 were quantified via PET imaging and Simoa assays, respectively, while APOE genotyping was performed using TaqMan assays. Microbial diversity, differential abundance analysis, and correlation mapping with neuropsychological and neuroimaging measures were conducted to identify gut microbiota species signatures associated with MCI and AD biomarkers. Results We identified 59 key microbial species linked to MCI and AD biomarkers. Notably, species within the same genera, such as Bacteroides and Ruminococcus, showed opposing effects, while Akkermansia muciniphila correlated with reduced amyloid burden, suggesting a protective role. Functional profiling revealed microbial pathways contributing to energy metabolism and neuroinflammation, mediating the relationship between gut microbes and brain health. Co-occurrence network analyses demonstrated complex microbial interactions, indicating that the collective influence of gut microbiota on neurodegeneration. Conclusions Our findings challenge genus-level microbiome analyses, revealing species-specific modulators of AD pathology. This study highlights gut microbial activity as a potential therapeutic target to mitigate cognitive decline and neurodegeneration. |
| format | Article |
| id | doaj-art-2741914ba13b4e71bf6847bfbcce48a5 |
| institution | OA Journals |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-2741914ba13b4e71bf6847bfbcce48a52025-08-20T02:00:07ZengBMCAlzheimer’s Research & Therapy1758-91932025-05-0117111810.1186/s13195-025-01769-9Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathologyKang-Chen Fan0Chen-Ching Lin1Yen-Ling Chiu2Seong-Ho Koh3Yi-Chien Liu4Yi-Fang Chuang5School of Medicine, National Yang Ming Chiao Tung UniversityInstitute of Biomedical Informatics, National Yang Ming Chiao Tung UniversityDepartment of Medical Research, Far Eastern Memorial HospitalDepartment of Neurology, College of Medicine, Hanyang University Guri HospitalDepartment of Neurology, Cardinal Tien HospitalSchool of Medicine, National Yang Ming Chiao Tung UniversityAbstract Background Emerging evidence highlights the bidirectional communication between the gut microbiota and the brain, suggesting a potential role for gut dysbiosis in Alzheimer’s disease (AD) pathology and cognitive decline. Existing literature on gut microbiota lacks species-level insights. This study investigates gut microbiota alterations in mild cognitive impairment (MCI), focusing on their association with comprehensive AD biomarkers, including amyloid burden, tau pathology, neurodegeneration, and cognitive performance. Methods We analyzed fecal samples from 119 individuals with MCI and 320 cognitively normal controls enrolled in the Taiwan Precision Medicine Initiative on Cognitive Impairment and Dementia cohort. Shotgun metagenomic sequencing was conducted with taxonomic profiling using MetaPhlAn4. Amyloid burden and plasma pTau181 were quantified via PET imaging and Simoa assays, respectively, while APOE genotyping was performed using TaqMan assays. Microbial diversity, differential abundance analysis, and correlation mapping with neuropsychological and neuroimaging measures were conducted to identify gut microbiota species signatures associated with MCI and AD biomarkers. Results We identified 59 key microbial species linked to MCI and AD biomarkers. Notably, species within the same genera, such as Bacteroides and Ruminococcus, showed opposing effects, while Akkermansia muciniphila correlated with reduced amyloid burden, suggesting a protective role. Functional profiling revealed microbial pathways contributing to energy metabolism and neuroinflammation, mediating the relationship between gut microbes and brain health. Co-occurrence network analyses demonstrated complex microbial interactions, indicating that the collective influence of gut microbiota on neurodegeneration. Conclusions Our findings challenge genus-level microbiome analyses, revealing species-specific modulators of AD pathology. This study highlights gut microbial activity as a potential therapeutic target to mitigate cognitive decline and neurodegeneration.https://doi.org/10.1186/s13195-025-01769-9Gut-brain axisGut microbiomeAlzheimer’s disease pathologyMild cognitive impairmentShotgun metagenomicsAmyloid PET |
| spellingShingle | Kang-Chen Fan Chen-Ching Lin Yen-Ling Chiu Seong-Ho Koh Yi-Chien Liu Yi-Fang Chuang Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathology Alzheimer’s Research & Therapy Gut-brain axis Gut microbiome Alzheimer’s disease pathology Mild cognitive impairment Shotgun metagenomics Amyloid PET |
| title | Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathology |
| title_full | Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathology |
| title_fullStr | Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathology |
| title_full_unstemmed | Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathology |
| title_short | Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer’s disease pathology |
| title_sort | compositional and functional gut microbiota alterations in mild cognitive impairment links to alzheimer s disease pathology |
| topic | Gut-brain axis Gut microbiome Alzheimer’s disease pathology Mild cognitive impairment Shotgun metagenomics Amyloid PET |
| url | https://doi.org/10.1186/s13195-025-01769-9 |
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