Fig. 6: Akkermansia muciniphila (A. muciniphila) modulates the microbial tryptophan metabolites profile of doxorubicin (DOX)-treated mice.

Principal component analysis of a fecal metabolites and b serum metabolites among the control, DOX, and DOX + AKK groups (n = 6). c Bar chart of significantly different KEGG metabolic pathways (based on serum metabolites) among the control, DOX, and DOX + AKK groups (n = 6). d Serum concentrations of metabolites in tryptophan metabolism (ArAT aromatic amino acid aminotransferase, IPyA indole-3-pyruvate, fldH phenyllactate dehydrogenase, ILA indole-3-lactic acid, fldBC phenyllactate dehydratase, acdA acyl-Coa dehydrogenase, IPA indole-3-propionic acid, TMO tryptophan 2-monooxygenase, TrD tryptophan decarboxylase, IAM indole-3-acetamide, IAA indole acetic acid, IAId indole-3-aldehyde) among three groups of mice (n = 6). e Spearman correlation analysis between the IPA levels and cardiac injury markers (LVEF left ventricular ejection fraction, LVFS left ventricular fraction shortening, LDH lactate dehydrogenase, CK-MB creatine kinase-MB) in mice from the three groups (n = 18). f Pairwise comparisons of tryptophan metabolites, with a color gradient denoting Spearman’s correlation coefficient. The correlation between the bacterial expression profiles and each metabolite was determined using partial Mantel tests. The edge width corresponds to Mantel’s R statistic for the corresponding distance correlations, and the edge color denotes statistical significance (n = 6). g Serum levels of IPA in all participants (anthracycline, AC: n = 14; non-anthracycline, nAC: n = 16). h Spearman correlation analysis between the serum IPA levels and relative abundance of A. muciniphila in all participants. Data presented as mean ± SD. For statistical analysis, two-way ANOVA with Tukey’s test for multiple comparisons was used. **P < 0.01, ***P < 0.001.