Inulin Diet Alleviates Abdominal Aortic Aneurysm by Increasing Akkermansia and Improving Intestinal Barrier.

Background/Objectives: Previous studies have shown varying efficacy of high-fiber diets containing different ingredients in abdominal aortic aneurysms (AAAs). This study aimed to identify which high-fiber diet protects against AAA in mice and elucidate the underlying mechanisms. Methods: This study compared inulin, cellulose, and chow diets in terms of their impact on aneurysm enlargement, elastin degradation, matrix metalloproteinase 2 and 9 expressions, CD3+ T cell and CD68+ macrophage infiltration, and macrophage differentiation. It also examined gut microbiota composition, focusing on Akkermansia, and evaluated intestinal barrier function and systemic inflammatory response. Results: The inulin diet, but not the cellulose diet, compared with the chow diet, reduced aneurysm enlargement, elastin degradation, matrix metalloproteinase 2 and 9 expressions, CD3+ T cell and CD68+ macrophage infiltration, and skewed macrophage towards M2 differentiation. The inulin diet enriched Akkermansia in both the small and large intestine. The inulin diet also enhanced the intestinal barrier by augmenting goblet cells, upregulating the gene related to the epithelial barrier and antibacterial peptides in the small intestine, and reducing circulating lipopolysaccharide and interleukin-1β levels. The inulin diet lowered the proportion of Ly6Chi monocytes and C-C chemokine receptor 2 expression on these cells in the bone marrow, reducing aneurysm infiltration. Administering Akkermansia to AAA mice decreased intestinal permeability and mitigated AAA. Conclusions: A diet rich in fermentable fiber inulin, as opposed to cellulose, alleviates AAA in mice. This beneficial effect is attributed to the enhanced presence of Akkermansia bacteria and improvement of the intestinal barrier.