KOBE, Japan, Dec. 9, 2022 In a study recently published in the journal Hypertension, researchers from Kobe University and Noster Inc. report the role of gut bacteria in the development of a fatal cardiovascular disease
While cardiac arrest and stroke are familiar cardiovascular concerns, a less common but equally fatal disorder is abdominal aortic aneurysm (AAA). AAA occurs when the aorta—the main blood vessel supplying the abdominal organs—swells and subsequently ruptures causing an internal bleed. Now, AAAs are difficult to diagnose as most patients do not show symptoms. What’s more, therapeutic options to prevent AAAs are underwhelming. Thus, more research on the clinical management of AAAs is required. In a recent collaboration between Kobe University and the gut bacteria–focused company Noster Inc., a team led by Tomoya Yamashita has revealed the importance of gut bacteria in the development of AAA.
The composition of bacteria normally residing in the gut is known to play a role in other cardiovascular diseases. To understand its involvement in AAA, the team used mice with hampered cholesterol metabolism. These mice were put at further risk for AAA by feeding them a high-cholesterol diet. Subsequently they were divided into three groups: one receiving intraperitoneal injections of antibiotics, one receiving antibiotics orally (administered by supplementing their water), and the last one receiving water only. After receiving antibiotic treatment or control, the mice were subjected to administration of Angiotensin II, a known chemical inducer of AAA.
As expected, the tissues of mice revealed that orally administered antibiotics greatly suppressed the gut microbiota whereas the injectable form (and water) did not. Mice receiving oral antibiotics also had the lowest incidence of AAAs and related deaths. Imaging showed that the aortas of these mice had the thinnest diameters while the other two groups had bulging counterparts. The suppression of gut bacteria was, thus, somehow leading to a reduced risk of AAA.
Oftentimes, the immune system also plays a role in cardiovascular conditions. Immune cells migrate to and accumulate in damaged areas causing severe inflammation. Hence, the involvement of immune cells was analyzed next. It was found that the oral antibiotic–receiving group had very low accumulation of monocytes, a type of white blood cells, in the aorta. When the sites of monocyte production (bone marrow) and storage (spleen and lungs) were investigated, marked depletion was found in the spleen but the other organs remained unaffected. The researchers then probed deeper, to discover that the suppression of gut bacteria in this group caused low levels of a protein known as the Nod1 ligand that typically activate receptors on the surface of immune cells. When Nod1 ligands were then injected into the mice, they started showing monocyte accumulation in their aortas, accompanied by bulging.
This study revealed the link between gut bacteria and the onset of AAA. This information is vital, given the lack of clinical manifestations or preventative strategies for AAA. “For the first time, we demonstrated that gut microbiota or bacterial signals could be new therapeuti[c] targets for AAAs,” concludes the research group. Lifestyle choices that impact gut health could have deeper impacts on heart health too.
Abdominal aortic aneurysm (AAA): AAAs are caused by a swelling in the abdominal portions of the aorta, the main vessel that carries blood from the heart. The walls of the aorta start thinning and bulging over time and eventually rupture if there is no timely intervention. The risk for AAA also increases with age. AAA also has clinical risk factors including high blood cholesterol levels and high blood pressure.
Since AAA has few external manifestations, the condition is often detected accidentally when a doctor recommends imaging tests for other ailments. Therefore, one of the best ways to counter AAA is to prevent it altogether. In this study, the researchers depict the involvement of gut bacteria in AAA and suggest that interventions that keep them in check can be a potential means to control AAA.
Ryohei Shinohara, Hitomi Nakashima, Takuo Emoto, Tomoya Yamashita, Yoshihiro Saito, Naofumi Yoshida, Taishi Inoue, Katsuhiro Yamanaka, Kenji Okada, Ken-ichi Hirata. Gut Microbiota Influence the Development of Abdominal Aortic Aneurysm by Suppressing Macrophage Accumulation in Mice. Hypertension, 2022
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