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

Abstract

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.

Anthocyanin-Rich Butterfly Pea Flower Extract Ameliorating Low-Grade Inflammation in a High-Fat-Diet and Lipopolysaccharide-Induced Mouse Model

“…Based on current scientific evidence, diet-induced metabolic endotoxemia can impair the gut integrity, leading to an inhibited growth of A. muciniphila. Increased abundance of A. muciniphila was associated with restoration of gut barrier function and prevention of adipose inflammation against HFD-mediated metabolic endotoxemia. , Since acetate producing Oscillospiraceae is directly associated with A.…”

“…56 Increased abundance of A. muciniphila was associated with restoration of gut barrier function and prevention of adipose inflammation against HFD-mediated metabolic endotoxemia. 56,57 Since acetate producing Oscillospiraceae is directly associated with A. muciniphila, BF supplementation at a high dose was shown to enhance their growth and hence the circulating acetate, resulting in improved insulin sensitivity of the host. 58−60 Furthermore, our results also indicated that BF supplementation can increase the abundance of Ruminococcaceae and Butyricicoccaceae (Figure 6F).…”

The gut microbiota in experimental abdominal aortic aneurysm

“…Previous studies have demonstrated that Akkermansia is a promising target for treating intestinal microbiota-related diseases, such as colitis, metabolic syndrome, and immune diseases (15). Recently, He et al (16) reported that Akkermansia muciniphila inhibited the formation of AAA by restoring gut microbiota diversity, and altered the expression of peripheral immune factors. Barnesiella intestinihominis is also regarded as a beneficial bacterium for host homeostasis.…”

Akkermansia muciniphila – multifunctional bacteria

“…[25] Different study shown that administration of A. muciniphila improved damage of the elastic fibers in the vascular wall, inhibited the infiltration of inflammatory cells and protected the integrity of the medial septum in the abdominal aorta of mice, indicating that A. muciniphila can inhibit the formation of aortic aneurysms in mice. [26] Nonalcoholic fatty liver disease (NAFLD) NAFLD is a chronic liver disease and a hepatic manifestation of the metabolic syndrome. The exact cause of NAFLD is unidentified, but it is thought to be linked with abnormal lipid metabolism associated with obesity and metabolic syndrome.…”