Searching for a Causal Link Between Gut Microbiome Populations and Pace of Aging
Mendelian randomization is a strategy for using genetic variants associated with specific phenotypes and outcomes to produce data supportive of a causal relationship between phenotype to outcome. Here, researchers aim to find evidence that larger populations of specific microbial species in the gut microbiome can speed up or slow down the process of degenerative aging, as assessed by aging clocks derived from simple health measures. The relative sizes of the microbial populations making up the gut microbiome shift with age, and research to date has demonstrated that the overall effects of these changes are negative: more pro-inflammatory microbes, fewer microbes producing beneficial metabolites. There are proven ways to produce lasting rejuvenation of the aged gut microbe, resetting the balance of populations, such as via fecal microbiota transplant from a young individual, but these interventions are not yet widely used.
Increasing evidence suggests that gut microbiota play an important role in the aging process. The gut microbiome, the collection of microorganisms inhabiting the human gastrointestinal tract, emerged as a key player in regulating host physiology and health. The gut microbiota begin to colonize the body from birth and develop together with the individual, playing a role in different stages of an individual's life. Accumulating evidence indicates that alterations in the gut microbiota composition and function, collectively referred to as dysbiosis, are associated with age-related diseases and may contribute to the aging process.
Observational studies cannot infer causal relationships between exposure and outcomes, and randomized controlled trial (RCT) studies often require a lot of research funding and costs and are constrained by experimental design limitations. Mendelian randomization (MR) uses genetic variation as an instrumental variable to infer causal relationships between exposures and outcomes from non-experimental data. Using MR has identified causal relationships between gut microbiota and aging-related diseases such as cardiovascular diseases and neurodegenerative diseases. MR studies also found causal relationships between gut microbiota and longevity. However, no MR studies have yet demonstrated a causal relationship between gut microbiota and biological aging.
In this study, two-sample MR was used to analyze the causal relationship between gut microbiota and biological aging in order to explore whether specific gut microbiota accelerate or decelerate the biological aging process and to provide new insights into promoting healthy aging through the modulation of gut microbiota. Streptococcus (β = 0.16) was causally associated with Bioage acceleration. Eubacterium (β = 0.20), Sellimonas (β = 0.06), and Lachnospira (β = -0.18) were suggestive of causal associations with Bioage acceleration, with the latter being protective. Actinomyces (β = 0.26), Butyricimonas (β = 0.21), and Lachnospiraceae (β = 0.24,) were suggestive of causal associations with Phenoage acceleration.
In conclusion, this Mendelian randomization study found that Streptococcus was causally associated with Bioage acceleration. Further randomized controlled trials are needed to investigate its role in the aging process.