Extended Data Fig. 7: Summary of study highlights.

Multi-omics analysis and metabolic modeling of aging mice revealed a decline in microbiome metabolic activity, reducing beneficial host-microbe and microbe-microbe interactions. Aging-related microbiome changes led to the accumulation of pro-aging metabolites (D-galactose, succinate) and a decline in beneficial metabolites (nucleotides, butyrate). These shifts correlated with increased systemic inflammation and downregulation of essential host pathways, like energy and nucleotide metabolism, which are involved in intestinal barrier function and cellular homeostasis.