Multi-omics integration reveals the link between gut microbiota dysbiosis, host metabolic dysregulation, and aortic inflammation in abdominal aortic aneurysm

An abdominal aortic aneurysm (AAA) is a localized expansion of the abdominal aorta, in which the vessel diameter exceeds 3 cm or is increased by more than 50% compared to the normal expected size. It has been increasingly recognized as a systemic disease involving complex interactions between vascular tissues and extra-aortic factors, particularly host metabolism and inflammation. The aim for the study was to integrate multi-omics approaches to systematically investigate the molecular mechanisms underlying AAA. Significantly reduced α-diversity Pielou’s evenness was observed in AAA mice with downregulated Bacteroides acidifaciens, Bacteroides caecimuris, Bacteroides fragilis and upregulated Roseburia sp₁XD42₆9, Chlamydia abortus, Eubacterium plexicaudatum, Eubacterium sp. 14₂. Additionally, the metabolic profiles of cecal contents and serum were significantly altered in AAA mice compared to those in sham mice, with synchronous enrichment of the primary bile acid biosynthesis pathway in both compartments. Notably, 17 metabolites exhibited coordinated alterations and significant positive correlations. Transcriptomics revealed activated inflammatory pathways (leukocyte recruitment and NF-κB signaling) and increased immune infiltration in AAA aortas. Integrated analysis further revealed impaired gut microbial amino acid metabolism, accompanied by intestinal accumulation of L-leucine and L-arginine. The levels of primary and secondary bile acids showed a distinct compartmental imbalance. Weighted gene co-expression network modeling revealed a significant inverse correlation between serum bile acid levels and aortic gene modules enriched in inflammatory/chemokine signaling and cell adhesion pathways. Multi-omics integration using DIABLO further identified a coordinated signature across transcriptomic, microbiomic, and metabolomic layers, distinguishing AAA from sham mice and revealing candidate biomarker features associated with AAA. AAA mice exhibited dysbiosis of the gut microbiota and alterations in the metabolic profile. Disrupted gut microbiota was associated with dysregulation of amino acid metabolism, whereas imbalanced bile acid metabolism was correlated with aortic inflammatory responses.