Background
Abdominal aortic aneurysm (AAA), a vascular disease with high disability and mortality, is associated with atherosclerosis and hypertension [
1]. An abnormal vascular inflammatory response and abnormal vascular structure trigger the onset of aortic aneurysms.
Recent studies have suggested that gut microbiota probably participate in host inflammation and the formation of atherosclerosis and hypertension [
2,
3]. Gut microbiota have been shown to be closely related to systemic inflammation by generating some toxic metabolic factors or by releasing lipopolysaccharides [
4]. Any factors that influence the intestinal microenvironment likely interrupt the balance in gut microbiota, ultimately leading to changes in the gut microbiome. For example, high choline intake elevates the level of blood trimethylamine oxide (TMAO), a metabolic factor that promotes cordial hypertrophy and ultimately increases the incidence of various cardiovascular- and cerebrovascular-related diseases [
5‐
9], while even changes in diet can change the gut miceobiome [
10‐
12]. All these factors can change the gut microbiome.
Therefore, focusing on the gut microbiome might provide some possible mechanism of AAAs. In this study, we applied Ang II-induced AAA to ApoE−/− mice and investigated alterations in the gut microbiome.
Discussion
In the present study, we found that abdominal aortic aneurysm (AAA) mice were subject to gut microbial dysbiosis. Although gut microbiome alterations emerged after the induction of AAAs, gut microbial dysbiosis likely inversely promoted the course of disease. Thus, exploring the gut microbiome in AAAs might provide some clues in the progress of AAAs.
First, we found that the gut microbial community was different between the AAA group and the corresponding control group. This result might be due to the challenge of angiotensin II, an endogenous, rigorous vasoconstrictor that can promote cardiac hypertrophy and impair vascular endothelial cells [
16]. The stimulation of Ang II might lead to vasoconstriction in the intestine and thus further interrupt the gut microbiome [
17]. Similar results were found in high blood pressure patients, as we found that the genus
Alistipes, harbored in HBP patients [
17], was positively correlated with the diameter of an AAA. However, our findings in the gut microbiome were not completely consistent with previous findings in a hypertension mouse model induced by Ang II [
17]. These differences might be due to the knock-out of the
ApoE gene, as gut microbiota interact with host genes [
18]. Another explanation is the different symbiotic bacteria in these studies, as different regions also influence the gut microbiome [
19].
We also found that
A. muciniphila, a newly identified probiotic reported in recent years [
20], was significantly reduced in the AAA mice. It is not surprising that
A. muciniphila might be involved in the progression of AAAs because it exerts beneficial effects in various diseases including atherosclerosis [
21] and dyslipidemia [
22]. Other studies also found that
Akkermansia decreased with increasing age in Tibetan minipigs [
23], and it was found to be induced by some types of traditional Chinese medicine [
24].
A. muciniphila is a kind of mucin-producing bacteria that can repair damage to the intestinal barrier in atherosclerosis models of ApoE
−/− mice [
21]. In addition, we previously found that exercise training could increase the abundance of
Akkermansia [
20]
. These results indicate that
A. muciniphila is likely essential in the host body and that it might be essential in the progress of AAAs.
In addition, a species belonging to
Helicobacter was also increased in AAA mice. This result was similar to that of our previous study in myocardial infarction mice, as
Helicobacter was negatively associated with left ventricular ejection fraction in MI mice [
20], indicating that
Helicobacter might be a common pathogen underlying some cardiovascular diseases.
The AAA model was established with a sustained infusion of angiotension II. Although previous studies have shown that the gut microbiome changes after challenge with angiotensin II or dyslipidemia, they have not investigated both of these effects. Additionally, AAA patients in the clinic always exhibit dyslipidemia and abnormal blood pressure. Nevertheless, further studies are still required to verify the function of these diseases.
There are still some limitations should be concerned. First, the mechanism of AAA seems more complicated in clinical practice rather than the abnormal of renin-angiotensin system or simply the deficiency of ApoE gene. Second, the reduction of A. muciniphila in AAA mice is an observational result, more data form human analysis is needed, and the underlying mechanisms of A. muciniphila should be investigated in the future.
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