2025/08/01 by Fabiana Grosso, Daniela Zanetti, Serena Sanna · 3 voices
Biochemistry, Genetics and Molecular Biology · Psychology · #Bioinformatics #Bioinformatics and Genomic Networks #Biology #Computational biology #Developmental psychology #Genetic Associations and Epidemiology #Gut microbiome #Gut microbiota and health #Microbiome #Psychology
paper · pdf · doi:10.18632/aging.206293
published in Aging 17(8), 1966-1987 (Impact Journals LLC)
openalex publication_date 2025/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
In the past 20 years, the involvement of gut microbiome in human health has received particular attention, but its contribution to age-related diseases remains unclear. To address this, we performed a comprehensive two-sample Mendelian Randomization investigation, testing 55130 potential causal relationships between 37 traits representing gut microbiome composition and function and age-related phenotypes, including 1472 inflammatory and cardiometabolic circulating plasma proteins from UK Biobank Pharma Proteomic Project and 18 complex traits. A total of 91 causal relationships remained significant after multiple testing correction (false discovery rate p-value <0.05) and sensitivity analyses, notably two with the risk of developing age-related macular degeneration and 89 with plasma proteins. The link between purine nucleotides degradation II aerobic pathway and apolipoprotein M was further replicated using independent genome-wide association study data. Finally, by taking advantage of previously reported biological function of Faecalibacterium prausnitzii we found evidence of regulation of six proteins by its function as mucosal-A antigen utilization. These results support the role of gut microbiome as modulator of the inflammatory and cardiometabolic circuits, that may contribute to the onset of age-related diseases, albeit future studies are needed to investigate the underlying biological mechanisms.