Fig. 6

Correlation network reveals specific links between the mucosal microbiome, microbiota-associated metabolites, and accelerated biological aging. A A heatmap displays the relative abundance of metabolites associated with gut health in both stool and plasma samples from PLWH on ART and PLWoH. The color gradient, from blue to red, signifies the normalized metabolite values, with red representing higher abundance and blue indicating lower abundance. Differences between groups were assessed using the Mann–Whitney U test. B Spearman’s rank correlation heatmap demonstrates relationships between gut-specific metabolites (rows) and indicators of accelerated biological aging, tight junction integrity, microbial translocation, and inflammatory markers (columns). The top panel highlights metabolites upregulated in PLWH on ART, while the bottom section presents metabolites that are downregulated in this group. Positive and negative correlations are represented by red and blue, respectively. Key: * P < 0.05, ** P < 0.01, *** P < 0.001. C Circos plots visualize Spearman’s rank correlations among tissue-specific microbiome (yellow), metabolites derived from plasma and stool samples (green), and indicators of accelerated biological aging specific to both tissue and blood (blue). Red lines denote significant positive correlations, while blue lines signify negative correlations. Only correlations manifesting a 3-way association are included. Emphasized lines hint at their potential functional relevance. 5-HIAA stands for 5-Hydroxyindole-3-acetic acid, K/T ratio stands for Kynurenine/Tryptophan ratio, and Q/T ratio stands for Quinolinic acid/Tryptophan ratio