Fig. 5: BHB produced via IPA-enhanced ketogenesis rescues LGR5+ ISC depletion.

a Temporal β-hydroxybutyrate (BHB) levels in cIECs post-DSS (n = 6). b Kinetics of Lgr5 expression in BHB-treated (40 mg/25 g) WT mice post-DSS (n = 6). c, d Quantification of LGR5+ cells/crypt (IFA) in DSS model (n = 6). e–j RE model analysis (16 Gy IR, n = 6): e Lgr5 (qRT-PCR); f, g LGR5 (IFA); h, i Histopathology (HE); j Tnfa, ZO-1, OCLN and Muc2 expression in ileum. k Lgr5 expression (qRT-PCR) in WT/Nlrp3-/- mice at D3 post-DSS (n = 6). l, m Hmgcs2/BHB levels in germ-free organoids ± IPA (n = 5). n Lgr5 expression (qRT-PCR) in germ-free organoids ± IPA/BHB (n = 5). o, q HMGCS2 expression/IFA in human organoids (n = 5). p BHB in human organoid supernatants post-IPA (200 μM, 6 h; n = 5). r–t LGR5 dynamics in human organoids post-cytokine injury with or without IPA/BHB pretreatment (n = 5). u, v qRT-PCR analyses of IL1B, IL8, TNFA, HES1, CTNNB1, LYZ and MUC2 in human organoids at 48 h post-injury (n = 5). Data represent mean ± SD from ≥2 independent experiments. Statistical significance determined by two-sided Student’s t-test or one-way ANOVA followed by Tukey’s post hoc test for multiple comparisons. Source data are provided as a Source data file.