Gut microbiota diversity and metabolomics analysis of curcumin's alleviation of abdominal aortic aneurysm progression.

Abdominal aortic aneurysm (AAA) is a high-risk vascular condition with a significant need for effective treatments to slow its progression, particularly for small-diameter AAAs. While previous studies have demonstrated curcumin's beneficial effects in AAA mouse models, the role of gut microbiota homeostasis and metabolic changes in this context remains poorly understood. We developed a recently established AAA mouse model and assessed alterations in the gut microbiota. We also examined the effect of curcumin on AAA progression. Fecal samples from different groups of mice were collected and analyzed using 16 s rRNA sequencing to explore the role of gut microbiota in curcumin's therapeutic actions, while serum samples were analyzed by LC-MS/MS to investigate metabolic changes associated with curcumin's therapeutic effects. In a mouse AAA model induced by elastase periadventitial incubation combined with β-aminopropionitrile (BAPN), we observed reduced gut microbiota diversity and a decrease in several probiotic genera. Curcumin treatment inhibited AAA progression, reduced pathological aortic changes and downregulated the expression of pro-inflammatory cytokines. Additionally, curcumin prevented the phenotypic shift of vascular smooth muscle cells from a contractile to a synthetic state. Notably, curcumin improved gut microbiota diversity, increased probiotic genera abundance. Finally, curcumin modulated the serum metabolic profile, alleviating AAA-related metabolic changes. Curcumin enhances gut microbiota homeostasis, modulates metabolic changes, and inhibits AAA progression, offering new insights into its therapeutic potential for AAA management.