Neuroscience · 2026
A Mendelian randomization study with bioinformatics analysis reveals gut microbiota mediates in heart failure and Alzheimer's disease via BAFF-R.
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Zhou Lv, Wang Zhitian, Jiang Ying, Wang Mengxue, Li Xiaoli, Ren Qingguo
Аннотация
BACKGROUND: The causal relationship between heart failure (HF) and Alzheimer's Disease (AD) is still debated, and the mechanisms underlying AD caused by HF are still not fully understood.
METHODS: This study aimed to explore the potential genetic causality between HF and AD using two-sample Mendelian randomization (MR) study. The investigation was extended with mediation MR to explore the underlying genetic mechanisms. Bioinformatics analysis provided additional evidence.
RESULTS: In our investigation, we harnessed a two-sample MR method to delineate a causal relationship between HF and AD, uncovering a significant positive association. Our results, derived from a meticulous two-step MR analysis, have shed new light on the mediating role of gut microbiota (GM) within the HF-AD interplay. Notably, we identified specific metabolic pathways with substantial correlations: a pivotal super-pathway crucial for the biosynthesis of branched chain amino acids (BCAAs) and the pyrimidine deoxyribonucleotides de novo biosynthesis II pathway. Our findings extend beyond the metabolic, revealing the 'BAFF-R on CD20-' immune cells as key mediators in the GM-AD pathway. Bioinformatics analysis revealed significant enrichment of common differentially expressed genes between HF and AD in immune-related pathways.
CONCLUSIONS: We present a thorough genetic analysis of the relationship between HF, AD, and the intestinal-neuroimmune interaction, emphasizing the potential of GM and immune cells as therapeutic targets.
METHODS: This study aimed to explore the potential genetic causality between HF and AD using two-sample Mendelian randomization (MR) study. The investigation was extended with mediation MR to explore the underlying genetic mechanisms. Bioinformatics analysis provided additional evidence.
RESULTS: In our investigation, we harnessed a two-sample MR method to delineate a causal relationship between HF and AD, uncovering a significant positive association. Our results, derived from a meticulous two-step MR analysis, have shed new light on the mediating role of gut microbiota (GM) within the HF-AD interplay. Notably, we identified specific metabolic pathways with substantial correlations: a pivotal super-pathway crucial for the biosynthesis of branched chain amino acids (BCAAs) and the pyrimidine deoxyribonucleotides de novo biosynthesis II pathway. Our findings extend beyond the metabolic, revealing the 'BAFF-R on CD20-' immune cells as key mediators in the GM-AD pathway. Bioinformatics analysis revealed significant enrichment of common differentially expressed genes between HF and AD in immune-related pathways.
CONCLUSIONS: We present a thorough genetic analysis of the relationship between HF, AD, and the intestinal-neuroimmune interaction, emphasizing the potential of GM and immune cells as therapeutic targets.