The composition of the gut microbiome changes with age, and researchers have demonstrated that many of these changes correlate with worse outcomes in aging. In animal studies, altering the composition of the gut microbiome to be more youthful produces health benefits, indicating that changes in the gut microbiome contribute to aging, but similar data in humans remains sparse. Mendelian randomization is a way to use genetic differences across a study population to infer whether or not a given correlation indicates causation. The results are not conclusive, but add support for causation to the be the case. Here, researchers mine a large database of gut microbiome composition, genetics, and health outcomes in an attempt to find specific cases in which an aspect of the gut microbiome, such as increased numbers of a given microbial species or altered production of a specific metabolite, is a contributing cause of an aspect of degenerative aging.
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 55,130 potential causal relationships between 37 traits representing gut microbiome composition and function and age-related phenotypes, including 1,472 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 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.
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