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

Abstract The Methionine restriction (MR) diet has been shown to delay aging and extend lifespan in various model organisms. However, the long‐term effects of MR diet on the gut microbiome composition remain unclear. To study this, male mice were started on MR and control diet regimens at 6 months and continued until 22 months of age. MR mice have reduced body weight, fat mass percentage, and bone mineral density while having increased lean mass percentage. MR mice also have increased insulin sensitivity along with increasing indirect calorimetry markers such as energy expenditure, oxygen consumption, carbon dioxide production, and glucose oxidation. Fecal samples were collected at 1 week, 18 weeks, and 57 weeks after the diet onset for 16S rRNA amplicon sequencing to study the gut microbiome composition. Alpha and beta diversity metrics detected changes occurring due to the timepoint variable, but no changes were detected due to the diet variable. The results from LEfSe analysis surprisingly showed that more bacterial taxa changes were linked to age rather than diet. Interestingly, we found that the long‐term MR diet feeding induced smaller changes compared to short‐term feeding. Specific taxa changes due to the diet were observed at the 1 or 18‐week time points, including Ileibacterium, Odoribacter, Lachnoclostridium, Marinifilaceae , and Lactobacillaceae . Furthermore, there were consistent aging‐associated changes across both groups, with an increase in Ileibacterium and Erysipelotrichaceae with age, while Eubacterium_coprostanoligenes_group, Ruminococcaceae, Peptococcaceae , and Peptococcus decreased with age.