Akkermansia muciniphila Alters Gut Microbiota and Immune System to Improve Cardiovascular Diseases in Murine Model

The gut microbiota plays an important role in a variety of cardiovascular diseases. The probiotics screened based on microbiota can effectively improve metabolism and immune function of the body, which is of great value in the field of cardiovascular disease treatment. Abdominal aortic aneurysms (AAA) refer to the lesion or injury of the abdominal aortic wall resulting in a localized bulge, which is one of the cardiovascular diseases with pulsing mass as the main clinical symptom. Previous studies have confirmed that A. muciniphila was depleted in the guts of AAA patients or mice. A. muciniphila is a potential probiotic for the treatment of intestinal microbiome-related diseases. Therefore, this study aims to investigate the effects of A. muciniphila on gut microbiota and disease-related biomarkers in AAA mice. C57BL/6J mice were used to construct the AAA model and treated with A. muciniphila. Aortic aneurysm formation in the AAA group is associated with the increased diameter of the abdominal aorta and inflammatory infiltration. A. muciniphila inhibited the formation of AAA and repaired tissue damage. The number of gut microbiota and α diversity index were decreased in the model group. A. muciniphila increased the number of gut microbiota and α diversity in AAA mice. The abundance of uncultured bacterium and Lactobacillus were increased, while the abundance of the Lachnospiraceae NK4A136 group was reduced in the AAA group. Compared with the control group, the levels of MMP-1, MMP-9, IL-33, CTSB, and CTSL in tissue and the levels of IL-6, IFN-γ, and CRP in blood were significantly increased, and the levels of IL-4, IL-10, and IL-17A in blood were significantly decreased in the AAA group. The intervention of A. muciniphila reversed these changes. The gut microbiota function prediction showed changes in E. coli, Clostridium, and Lactobacillus metabolism-related functional pathways. Akkermansia was negatively correlated with Helicobacter and Lactobacillus and positively correlated with Clostridium_sensu_stricto_1 and Escherichia shigella at the genus level. In conclusion, A. muciniphila inhibited the formation of AAA by restoring gut microbiota diversity, altering the expression of peripheral immune factors, and the functions of E. coli, Clostridium, and Lactobacillus, which may provide a new theoretical basis for the application of probiotics in cardiovascular diseases.