Long term methionine restriction: Influence on gut microbiome and metabolic characteristics

Area of Science:

• Gerontology
• Microbiology
• Nutritional Science

Background:

• Methionine restriction (MR) is known to extend lifespan and delay aging in model organisms.
• The long-term impact of MR diets on the gut microbiome remains largely uncharacterized.
• Understanding these effects is crucial for potential human health applications.

Purpose of the Study:

• To investigate the long-term effects of a methionine restriction (MR) diet on the gut microbiome composition in aging male mice.
• To compare the influence of diet versus aging on microbial diversity and specific taxa.
• To assess whether short-term or long-term MR diet feeding elicits more significant microbiome alterations.

Main Methods:

• Male mice were fed either an MR diet or a control diet from 6 to 22 months of age.
• Physiological parameters including body weight, body composition, and insulin sensitivity were monitored.
• Fecal samples were analyzed using 16S rRNA amplicon sequencing at multiple time points (1, 18, and 57 weeks) to assess gut microbiome composition.

Main Results:

• MR diet led to reduced body weight, fat mass, and bone mineral density, alongside increased lean mass and insulin sensitivity.
• Gut microbiome diversity (alpha and beta) showed changes related to aging (timepoint) but not the MR diet itself.
• Bacterial taxa shifts were predominantly associated with age rather than diet, with long-term MR showing fewer changes than short-term MR.

Conclusions:

• While the MR diet confers physiological benefits in aging mice, its long-term impact on gut microbiome composition is minimal compared to the effects of aging.
• Aging itself drives significant alterations in the gut microbiome, independent of methionine restriction.
• Short-term MR diet interventions may induce transient microbial changes, but these effects diminish with prolonged dietary adherence.