Fig. 2: Bioavailability of gut microbiota-dependent indole-based AHR ligands was disrupted after stroke. | Nature Communications

Fig. 2: Bioavailability of gut microbiota-dependent indole-based AHR ligands was disrupted after stroke.

From: Benefits of equilibrium between microbiota- and host-derived ligands of the aryl hydrocarbon receptor after stroke in aged male mice

Fig. 2

a Metabolomics analysis of plasma samples from wild-type (WT) and germ-free (GF) mice. Host-derived metabolites (tryptophan [Trp] and Kynurenine [Kyn]) did not differ between WT and GF plasma samples. However, indole-3-carboxaldehyde and indole-3-propionate concentrations were significantly reduced in GF plasma (n = 5/grp). b Metabolomic analysis of brains revealed specific indole-based AHR ligands that depend on the presence of a microbiota. Indole-3-carboxaldehyde (p = 0.0122) and indole-3-propionate (p < 0.0001) were undetectable in GF brains relative to WT control brains, while Trp and Kyn concentrations did not differ (n = 5/grp). c1 Major bacterial populations involved in the regulation of AHR ligands and Trp metabolism (such as phylum Actinobacteria predominant genus being Bifidobacteria) were significantly (Mann–Whitney test: p < 0.001614, FDR-Adi.p < 0.003766; overall Median: 0.08179) reduced by aging and experimental stroke in aged WT mice. c2 No significant differences (Observed OTUs: p < 0.7 and Shannon: p < 0.54) in alpha diversity (measures within sample diversity) and operational taxonomic units (p = 0.7 or 0.5) between the groups were observed. d Principal component analysis plot of 16S data shows a significant (p = 0.002) clustering effect of stroke animals relative to the sham group. e The LDA score clearly shows changes in bacterial families in stroke versus sham animals. f Cladogram visualization of 16S data shows a clear pathological shift in bacterial diversity in stroke animals relative to healthy sham animals. g Metabolomics analysis of aged WT brain and plasma samples at multiple timepoints post-stroke (n = 5/grp). Kyn concentrations increased while concentrations of indole-3-carboxaldehyde and indole-3-propionate were significantly decreased in both brain and plasma (n = 5/grp). h Metabolomic analysis of aged WT plasma samples shows increased concentrations of Kyn at 3 days post-stroke and no significant difference between groups at 30 days post-stroke (n = 5/control, 6/treated). Concentrations of indole-3-carboxaldehyde and indole-3-propionate (p = 0.0182) were decreased at 3 days post-stroke (n = 5/control, 6/treated). Unpaired two-tailed t-tests were used for statistical analyses (a, b, h). All data (with error bars) are presented as mean ± SEM. All data points (each dot represents) presented are biological replicates.

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