Gut microbiota and epigenetic age acceleration: a bi-directional Mendelian randomization study

Area of Science:

• Genetics
• Microbiology
• Aging Research

Background:

• The gut microbiota's role in aging is recognized, but its genetic underpinnings concerning epigenetic age acceleration (EAA) remain underexplored.
• Investigating genetic links between gut microbial composition and biological aging markers is crucial for understanding aging mechanisms.

Purpose of the Study:

• To explore the association between gut microbiota and epigenetic age acceleration (EAA) using Mendelian randomization (MR).
• To identify specific gut bacteria that may causally influence EAA.

Main Methods:

• Utilized genetic instruments for gut microbiota from the MiBioGen consortium and the Dutch Microbiome Project.
• Employed four MR methods (IVW, MR-Egger, WMA, weighted mode) to assess causal relationships between gut microbiota and EAA.
• Conducted sensitivity analyses to address heterogeneity and horizontal pleiotropy.

Main Results:

• Identified potential causal associations between 12 bacterial taxa and EAA (P < 0.05).
• Found a positive association between *Holdemania_unclassified* and GrimAge acceleration (OR: 1.31).
• Observed negative associations for family *Acidaminococcaceae* (OR: 0.64) and family *Clostridiaceae1* (OR: 0.69) with GrimAge acceleration.
• Reverse MR revealed associations between EAA and 6 bacterial taxa, including an inverse association between Phenoage acceleration and genus *Turicibacter* (OR: 0.928).

Conclusions:

• The study suggests potential causal effects of specific gut microbiota on epigenetic age acceleration.
• Findings may offer novel targets for aging prevention strategies focused on modulating gut microbiota.