Connie: Good evening, dear friends. It’s great to have you here with us this evening. Today, we invited Dr. Hofstadter to our program. Thank you for joining us, Dr. Hofstadter.
Dr. Hofstadter: Thanks for inviting me. I’m excited to be here. Hello, everyone.
Connie: Cardiovascular diseases are the primary source of worldwide mortality. According to the world health organization, approximately 31 percent of global death was caused by cardiovascular diseases, out of this 85% were due to heart attack and stroke back in 2016. It was also predicted that, by 2030, cardiovascular diseases will affect around 23.6 million people over the globe. Today, we are going to discuss the relationship between probiotics and cardiovascular diseases. And before we get into today’s topic, would you like to give an introduction on cardiovascular diseases?
Dr. Hofstadter: Good idea. Cardiovascular disease is a metabolic syndrome, which is associated with risks like the increased ratio of low-density to high-density lipoprotein, increased triglyceride-rich lipoproteins, inflammation, and autoimmune neural dysfunction. Some contributing factors for cardiovascular diseases are genetic composition, high body mass index and medical history of an individual. This risk can be reduced by changing eating habits, sedentary lifestyles, and reducing consumption of tobacco and alcohol. Unhealthy lifestyles and food habits have a direct negative effect on the diversity and activity of gut microbiota.
Connie: And to put it in simple terms, what is the relationship between gut microbe and cardiovascular disease?
Dr. Hofstadter: Well. I think after all these episodes, everyone should know that the gut microbe is a large and diverse microbial community that resides in the human GI tract. It contains 15,000 to 36,000 bacterial species. The total number is about 10 times the total number of human cells. It regulates host metabolic activities and regulates the intestinal tract. The important microbiota of the immune barrier and biological barrier is closely related to cardiovascular diseases. Disturbance of the gut microbe can destroy the normal metabolism of the body, enhance the oxidative stress response in the body, and exacerbate systemic inflammation through the translocation of endotoxin to the systemic circulation. It’s one of the important factors in the occurrence and development of cardiovascular diseases. The changes in hemodynamics of patients with cardiovascular disease can further change the shape, function, and composition of the gut microbes in their intestines, and exacerbate the disease. In general, you can imagine that gut microbiota is linked not only to pathogenic invasion in the intestine but also to extraintestinal ailments, such as cardiovascular disease, diabetes, and obesity.
Connie: That makes sense. According to your description, gut microbiota can be a potential treatment and prevention for metabolic disease. So my next question is, probiotics target various pathways that lead to the development of cardiovascular diseases. What is the mechanism of this process?
Dr. Hofstadter: Well. Let me put it simply. Probiotic plays an important role in endothelial dysfunction and oxidative stress. Also, they can directly affect the onset of hypercholesterolemia and coronary heart disease through their metabolites such as bile acids, steroids, short-chain fatty acids, and trimethylamine oxide. The third mechanism is that probiotics and their metabolites can reduce the symptom of hypertension. And finally, they play an important role in autonomic control of cardiovascular function as well.
Connie: I suppose that maybe we can start from the first mechanism. I have found that numerous studies recommended that the consumption of probiotics can positively influence the functionality of the endothelial layer. Remind us what exactly is endothelium?
Dr. Hofstadter: Sure. In general, the endothelium is a cell’s vascular layer. It not only serves as the primary barrier between vascular muscles and bloodstream and tissue spaces, but also allows selective passage of solutes, fluids, inflammatory molecules, growth factors, et cetera. Endothelial cells have various roles, including regulating vascular tone through synthesis or release of vasodilator or vasoconstrictor, releasing of inflammatory molecules, releasing reactive oxygen species, regulating the immune response. It also participates in maintaining blood homeostasis, platelet aggregation, regulating antithrombotic and prothrombotic balance.
Connie: I see. So any adverse change in endothelial cells can lead to disturbance in their functioning, and result in diseased conditions. Endothelial dysfunction is accepted as a major risk factor in classic cardiovascular disease mechanisms. But what does endothelial dysfunction specifically refer to?
Dr. Hofstadter: Well, Endothelial dysfunction is characterized by reduced endothelium-mediated vasorelaxation, disturbance in hemodynamic regulation, reduced fibrinolytic ability, excessive release of growth factors and reactive oxygen species, enhanced expression of adhesive proteins, and inflammatory genes, increased oxidative stress, and increased cell layer permeability. There have been numerous studies suggesting the consumption of probiotics can positively influence the functionality of the endothelial layer.
Connie: I can give our listeners some examples. The application of the probiotic formulation to rats having endothelial dysfunction of mesenteric artery ring with common bile duct ligation has been shown to improve the pathological condition of the rat. Another study also showed that Lactobacillus coryniformis probiotic treatment improved the endothelial functioning and lipopolysaccharide-induced vascular oxidative stress in control mice. The oral administration of probiotic drink for 56 days could repair the structure of vascular endothelium, decrease oxidative stress and increase nitrogen oxide bioavailability to rats. It also resulted in the recruitment of endothelial progenitor cells and diminished endothelial dysfunction.
Dr. Hofstadter: I just wanted to add to your examples. Various researchers observed that lactic acid bacteria were able to partially reverse the relaxation deficit of the aorta and increase the nitric oxide level in spontaneous hypertension rats. They also observed that probiotic administration improved endothelial function by reducing vascular oxidation and inflammation. Also, the intake of the probiotic consortium was reported to be able to establish a normal gut microbiome and improve endothelial functioning, leading to reduced vascular pro-inflammation and pro-oxidation. The probiotic consortium includes Lactobacillus fermentum and Lactobacillus coryniformis with Lactobacillus gasseri. Furthermore, clinical trials on human and human cell lines had also shown the positive impact of probiotics on endothelial functioning. A recent report showed that Lactobacillus Plantarum or Streptococcus thermophilus fermented soymilk increased nitric oxide production and nitric oxide synthase activity, signifying their impact in enhancing endothelial function.
Connie: That’s a lot of studies on probiotics’ impact on endothelial functioning. Next, I want to talk about probiotics in hypercholesterolemia. Let’s first review what cholesterol is. Simply put, cholesterol is a vital constituent of body tissues. But the elevated blood cholesterol can cause a major threat to coronary heart problems. Hypercholesterolemia and dyslipidemia are the most common cause of most cardiovascular diseases. Now that’s clear. Dr. Hofstadter, can you let us know what is the relationship between probiotics and cholesterol?
Dr. Hofstadter: In general, the adhesion of probiotic bacterial cells to the epithelial layer of the intestine can lower cholesterol levels in the body.
Connie: What are the mechanisms of probiotics helping in lowering cholesterol levels?
Dr. Hofstadter: Hmm, there are three mechanisms of action that have been proposed. The first one is that probiotics can transfer cholesterol to bile acid hydrolysis via microbial bile salt hydrolase enzyme. Secondly, probiotics can help cholesterol incorporation in the microbial cell. And finally, cholesterol conversion to easily assimilated metabolite.
Connie: That’s easy to understand. And I heard that some researchers also suggested that probiotics were able to lower the cholesterol biosynthesis in the liver. In addition. various studies showed positive effects of probiotics on cholesterol levels in the body. We have also seen research that observed attachment or assimilation of cholesterol on L. acidophilus surface, thus showing hypercholesterolemic ability. Another research also observed a significant reduction in triglyceride, low-density lipoprotein, and total cholesterol with the administration of Bifidobacterium fermented milk.
Dr. Hofstadter: You have read many research articles as well. These effects that you mentioned were further confirmed by another group of researchers by feeding B. lactis or B. longum fermented yogurt to the rats. And have you also seen recent research that reported an efficacious and safe application of encapsulated Lactobacillus reuteri. They had active bile salt hydrolase enzyme fermented yogurt formulation in decreasing low-density lipid cholesterol, total cholesterol, apolipoprotein B-100, and non-high-density lipid cholesterol in the hypercholesterolemic organism.
Connie: Certainly. Hypertension can cause several pathological conditions such as heart failure, cardiac stroke, acute myocardial infarction, failure of the renal system, and the main cause of premature death worldwide. Primary or essential hypertension depends upon various genetics, demographic and environmental conditions of the individual. Secondary hypertension is originated from behavioral conditions including drugs, smoking, et cetera, endocrine disorders, cancer, and excessive activation of the renin-angiotensin system. So, what is the relationship between probiotics and hypertension?
Dr. Hofstadter: So probiotics and their metabolites can improve total cholesterol level, low-density lipoprotein /high-density lipoprotein ratio, blood glycemic levels, insulin resistance, and functioning of the renin-angiotensin system. They were confirmed to secrete various effective bioactive metabolites having angiotensin-converting enzyme inhibition activity that can be targeted for the management of high blood pressure.
Connie: But why inhibition of angiotensin-converting enzyme can reduce high blood pressure?
Dr. Hofstadter: It’s a good question. In the renin-angiotensin system, renin causes the inactivation of angiotensinogen via hydrolyses, resulting in inactive angiotensin-I, which is enzymatically converted by the angiotensin-converting enzyme to angiotensin-II. Then Angiotensin-II can cause increased blood pressure and vasoconstriction. So, inhibition of angiotensin-converting enzymes can serve as a clinical target for the management of high blood pressure. What’s more is that various probiotic fermented foods including milk, yogurt, cheese, ice-creams, soymilk have angiotensin-converting enzyme inhibitory peptides. Various clinical studies on humans also validated probiotics’ ability to reduce high blood pressure levels. A significant reduction in blood pressure was observed with oral administration of Lactobacillus Plantarum. Clinical trial-based meta-analysis showed that probiotic consumption markedly reduced blood pressure in high blood pressure patients.
Connie: That is amazing. And finally, researchers also reported that probiotics can benefit the autonomic neural control of cardiac pacemaker, baroreflex, thereby controlling heart rhythm from brainstem integrative areas.
Dr. Hofstadter: Exactly. Supplementing kefir for at least 8 weeks can reduce and incompletely reverse abnormal cardiac sympathetic predominance over the parasympathetic tone in spontaneous hypertension rats. Some studies showed that probiotics were significantly linked with reduced production of intravascular reactive oxygen species and increased nitric oxide bioavailability. Reduction in cytokines and reactive oxygen species production in the hypothalamic paraventricular nucleus might be a fundamental mechanism of probiotics on cardiac autonomic control that reduced hypertension and organ damage. Probiotics can cause increased levels of anti-inflammatory molecules, which diminish hypertension and organ damage, so that regular functioning of the parasympathetic or sympathetic system can be restored.
Connie: Let me briefly summarize what we have talked about today. In recent years, with the in-depth research on cardiovascular diseases and intestinal microecology, the relationship between cardiovascular diseases and gut microbes has gradually been recognized, providing a new direction for the treatment of cardiovascular diseases. Specifically, the morphology and function of the intestinal tract of patients with cardiovascular diseases are affected, leading to disorders of the gut microbe, disrupting the normal metabolism of the body, and enhancing the oxidative stress response and systemic inflammation in the body. This series of changes can exacerbate intestinal disease and intensify flora disorder, which makes patients with cardiovascular diseases suffer from long-term and increasingly severe inflammatory reactions, and even increases the risk of other diseases.
Dr. Hofstadter: Exactly. So the prevention and treatment of cardiovascular diseases can start from regulating the gut microbe, and diet is an important factor affecting the structure and function of the gut microbe, and it is also a basic means for regulating the gut microbe. High-fiber, high-protein, and foods rich in carbohydrates and polyphenols can increase the diversity of the flora, balance the structure of the flora and enhance its metabolic function, thereby alleviating inflammation.
Connie: Probiotics directly or indirectly enhance the normal functioning of various cardiovascular diseases. The administration of probiotics has promising therapeutic effects on the cardiovascular system, so it can be used as an alternative approach to treat cardiovascular diseases. I hope you enjoyed today’s episode. Thanks, Dr. Hofstadter, for your time and input. And thanks everyone for listening. We will continue our discussion at the same time next Saturday. See you then!