Impact of Microbiome‐Immune Interplay on Cognitive Impairment: An Investigation from the MiaGB Cohort
Bibliographic record
Abstract
BACKGROUND: Alzheimer's disease (AD) pathogenesis has been linked to the microbiota-immune-brain axis; however, the relationship between gut microbiota, immune activity, and cognitive impairment remains unclear. Thus, this study examines the connection between intestinal microbial composition, immune cell phenotype, and cognitive function in older adults. METHOD: Data and biological samples were obtained from participants aged ≥60 years (Control, n = 30; mild cognitive impairment (MCI), n = 30) from the MiaGB (Microbiome in Aging Gut and Brain) consortium, a multi-site, clinical study. Cognitive function was assessed using Montreal Cognitive Assessment (MoCA) scores, immunophenotyping through flow cytometry, stool microbiome analysis using whole-genome metagenomics, and bulk transcriptomics analysis was carried out. RESULTS: The abundance of immune cells such as granulocytes, lymphocytes, T-cells, and NK cells was significantly decreased in MCI group. Interestingly, the levels of CD4+ were reduced while CD8+ cells increased in MCI participants compared to controls. Microbial profiling revealed distinct bacterial signatures, with MCI participants showing higher relative abundances of Eubacterium hallii, Parabacteroides distasonis, Eggerthella_sp_CAG_298, Dorea formicigenerans and Alistipes finegldii. Differential expression analysis of transcriptomics data identified 1632 upregulated and 240 downregulated genes. Gene ontology and pathway analysis revealed that upregulated genes are involved in several immune functions such as response to stimulus, adaptive immune response, lymphocyte, and T cell activation, while downregulated genes are linked to nervous system functions and signaling processes such as neuron projection. Transcriptomics analysis further highlighted that several downregulated genes are involved in the key pathways that participate in the neural functions. CONCLUSION: These distinct bacteria, immune cells, and gene expression profiles suggest that alterations in immune cell populations, gene expression, and gut microbiota are associated with cognitive function in aging, highlighting potential interactions between the microbiota-immune-brain axis and cognitive impairment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".