FMT-YA mice harbored a distinct metabolite landscape compared with FMT-AA mice. (A) PCA analysis to compare gut metabolome between FMT-AA and FMT-YA mice. (B) Volcano plot for differentially metabolites between FMT-AA and FMT-YA mice. (C) Heatmap showing the differentially produced metabolites between FMT-AA and FMT-YA mice. (D) Metabolite set enrichment of upregulated metabolites in FMT-YA mice compared with FMT-AA mice. (E) The flowchart of metabolite intervention. Aged mice were treated with different metabolites for 4 weeks and then the number and function of HSCs were evaluated. (F) Absolute numbers of LT-HSCs in BM in the control, tryptophan, and I3C groups. (G) Number of total colonies measured for LT-HSCs in methylcellulose. (H) Donor-derived CD45.2⁺ reconstitution in CD45.1⁺ mice at 16 weeks after HSC transplantation. (I) Absolute cell numbers of donor-derived HSPCs in BM from recipient mice in HSC transplantation assay. (J) Bar graphs showing the BM serum concentrations of IL-1β, IL-5, and CXCL1. Graphs show mean ± SEM, with statistical significance determined by Student t test (n = 6 per group). ∗P < .05, ∗∗P < .01. FC, fold change.