Figure 8.

Dietary celastrol beneficially alters the gut microbiota

(A–I) DIO mice (n = 7 for each group) or HFD-fed lean C57BL/6 mice (n = 10 for each group) were subjected to oral administration of celastrol (3 mg/kg/day). Mouse fecal samples were taken and subjected to 16S rRNA gene sequencing. (A and G) PCoA of Bray-Curtis dissimilarity for all samples from (A) DIO mice treated with celastrol or (G) early celastrol-treated HFD-fed lean mice. (B and H) Stacked bar graph showing the relative abundance of bacterial taxa (genus level) of samples from (B) DIO mice treated with celastrol or (H) early celastrol-treated HFD-fed lean mice. (C and I) Significantly different intestinal microbiota at the genus level (C) among lean, DIO, and celastrol-treated DIO mice (n = 7 for each group) or (I) among lean, HFD and early celastrol-treated mice on an HFD (treated at the beginning of HFD) (n = 10 for each group). (D–F and J–L) The top 20 microbial species with significant changes in (D–F) DIO mice treated with celastrol or (J–L) early celastrol-treated HFD-fed lean mice. (M–N) Principal coordinate analysis (PCoA) of all KOs that were significantly altered by celastrol treatment in (M) DIO mice or (N) early celastrol-treated HFD-fed lean mice. (O–P) Pathway enrichment analysis of all significantly altered KOs in (O) DIO mice treated with celastrol or (P) early celastrol-treated HFD-fed lean mice. Error bars represent the mean ± SEM. p values were determined by ANOVA. 0.01<∗p < 0.05, 0.001<∗∗p < 0.01, 0.0001< ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001. ND, normal diet; HFD, high-fat diet; HFDC, high-fat diet supplemented with celastrol.