Metabolites and the Microbiota that Circulate: Understanding of Cardiovascular Condition

Bryndis Benediktsdottir^*
*Correspondence: Bryndis Benediktsdottir, Department of Cardiology, Central Adelaide Local Health Network, Adelaide, Australia, Email:

Introduction

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. It is anticipated that the annual death toll from CVDs will reach 23.3 million by 2030. In 2019, cardiovascular disease was the cause of death for 9 million people; accounting for almost a third of all deaths worldwide. Various risk factors, including age, gender, family history, hypertension, diabetes, obesity, smoking, and stress, contribute to the development of the disease. Atherosclerosis and myocardial infarction (MI) are on the rise worldwide due to rapid environmental changes and modern lifestyle factors, such as high meat consumption, a lipid-rich diet, and lack of physical activity. However, a meta-analysis of prospective cohort studies found no correlation between CVD and saturated fat intake, indicating that other environmental factors are to blame. Numerous essential functions are performed by the blood that flows continuously through our veins and arteries to ensure our survival. Due to the long-held belief that healthy people's bloodstream is sterile and that the blood is an unfavorable compartment for the microbes due to its bacteriostatic and bactericidal components6, recent studies, particularly cross-sectional studies targeting the SrRNA gene, have revealed a dominant group of blood-borne bacterial phyla (i.e., Proteobacteria, followed by Actinobacteria, Firmicutes, and Bac In addition, examination of the bacterial taxa reported in these studies reveals similar blood microbiota compositions, with Proteobacteria dominating (relative abundance values typically ranging from 85 to 90 percent) and Firmicutes, Actinobacteria, and Bacteroidetes present to a lesser extent. This suggests the existence of a core blood microbiome profile that persists regardless of the study environment or analytical method [1].

Numerous studies on the relationship between human health and disease and blood microbial composition have been published in the last two years. Microbial metabolites in the gut include amino acid derivatives, hormones, short-chain fatty acids (SCFAs), vitamins, and antioxidants, which may be absorbed directly into the patient's circulatory system. Furthermore, several recent studies demonstrated that the tissue microbiome plays a significant role in the onset of pre-diabetic and type 2 diabetic patients, COVID-19, metabolic diseases, portal hypertension, polycystic ovary syndrome, myocardial infar The current study aimed to summarize the intricate interplay between blood microbiota, circulating metabolites, and their putative roles in the development and progression of cardiovascular disease (CVD). For instance, an association between endotoxemia (elevation of endotoxin from gram-negative bacteria in the blood) and atherosclerosis was discovered in a population-based study several decades ago. More recently, the detrimental effect of a bacterial metabolite, trimethyl amine oxide [2].

Two decades ago, a study discovered bacterial S rRNA in healthy human blood, but the bacteria's final processes and presence had not been investigated. However, in recent years, a study used quantitative polymerase chain reaction to sequence 16 S rRNA gene V3-V4 hypervariable regions in the blood of 30 young healthy volunteers to investigate the blood microbiome composition in the different fractions. Different microbial communities exist within the digestive tract, on the skin surface, and nearly every visible surface of the Bacterial DNA was most abundant in the buffy coat (93.74%), followed by RBCs (6.23%) and plasma (0.03%). Microbial DNA is frequently found in cellular components in healthy people, and the microbial community composition of the healthy gut and blood showed significant alteration. In the gut, Firmicutes and Bacteroidetes phyla predominated, while Proteobacteria dominated in the blood. Healthy human circulating bacteria are considered dormant because they do not cause issues like sepsis and inflammation. These results indicated that the blood microbiota is predominantly translocated from the gastrointestinal However, the circulating microbiome plays a crucial role in natural physiology and immunology. Additionally, more research is required to gain a better understanding of the blood microbiota's role in physiology, immunity, and health [3].

Circulating microbial metabolites

The diversity of functional genes in the microbiota shows that the human microbiota is more capable of metabolism than human cells. Host systems only partially digest dietary compounds and other substances; the remainder is processed by gut bacteria, particularly in the large intestine's anaerobic environment. The gut microbiota should be taken into account when developing toxicological risk assessment methodologies for medications and environmental toxins. Our microbial cells metabolize a variety of compounds through proteolysis, reduction, hydrolysis, functional group removal, N-oxide cleavage, denitration, deconjugation, amine formation, amide hydrolysis, thiazole ring-opening, acetylation, and isoxazole scission. Trimethylamine N-oxide (TMAO) has received a lot of attention among microbial metabolites as a significant cause of cardiovascular disease (CVD). Various enzymes are involved, including azoreductases, esterases, lipases, nitroreductases, -glucuronidases, sulfatases, and –lyases. Studies on human cohorts and germ-free mice have found a direct correlation between elevated CVD risk and plasma TMAO levels. Intestinal microbiota suppression or food supplement depletion can stop TMAO production and lessen atherosclerosis in mice fed choline- and carnitine-rich diets, which resulted in high plasma TMAO levels and the development of atherosclerotic plaques. Therefore, circulating TMAO may serve as a helpful CV People who use broad-spectrum antibiotics experience gut microbiota depletion and have large decreases in TMAO levels. Additionally, people are advised to limit their intake of foods high in carnitine, choline, and lecithin since diet is a primary source of TMAO to lower the probability of developing a CVD. In addition, elevated TMAO levels may indicate increased risks of heart failure, peripheral artery disease, stroke, and stable coronary artery disease The TMAO receptor PERK in the endoplasmic reticulum has been discovered. It is interesting to note that TMAO has been shown to protect hemodialysis patients with vascular damage, possibly in part because of its inhibitory effects on AGE. It has been noted that several choline analogs lower TMAO levels in the blood. Experimental evidence in animals has shown that TMAO affects vascular dysfunction, inflammatory reactions, and oxidative stress through contributing pathways. The The microbial choline TMA lyase activity is inhibited by the natural substance 3,3-dimethyl-1- butanol, which is abundant in red wines, vinegar, and various grape seed oils. There is evidence that several choline analogs, such as fluromethylcholine, chloromethylcholine, bromomethylcholine, and iodomethylcholine, are more effective TMA lyase inhibitors that can lower plasma TMAO levels. This substance could prevent the formation of atherosclerotic lesions in Apoe/ mice without affecting blood cholesterol level [4].

Complex carbohydrates found in dietary fiber cannot be digested by the human intestine to support cell functions. Short-chain fatty acids However, fibers can be utilized by gut bacteria during the fermentation process, resulting in the production of SCFAs, which are saturated fatty acids with one to six carbon chains. The majority of SCFAs in the human body can be found in the forms acetate, propionate, and butyrate. SCFAs are important for controlling gluconeogenesis, lipid metabolic pathways, and anti-inflammatory responses. In addition, these substances, particularly butyrate, are thought to supply intestinal epithelial cells with energy [4].

Microbiota-targeted therapeutics

Modern methods like metabolomics and next-generation sequencing are being used to find changes in the blood microbiota and circulating metabolites. These biomarkers will be easier to incorporate into routine clinical analysis as biosensors and nanosensors for the detection of specific bacteria or their metabolites advance. As an alternative treatment option, a variety of methods have been used to restore the blood microbiota and circulating metabolites. To fix the digestive boundary and reestablish the equilibrium of the blood microbiota, prebiotics, probiotics, and anti-microbials have all been used, reestablishing the variety of the microorganisms in the stomach, which might immensely affect the blood microbiota and its flowing metabolites. Hemodialysis, a treatment for kidney disappointment that is frequently utilized, might be a remedial procedure to help unhealthy individuals' blood microbiotas fix. It is possible to precisely filter intestinal microbes and their derivatives through hemodialysis membranes. Small synthetic chemical compounds are being developed into drugs that target the microbiota, their metabolites, and host mediators, for instance. Using the oral charcoal adsorbent, indoxyl sulfate elimination from patients with advanced renal failure has been clinically performed a portion of these are presently in clinical preliminaries [3].

Discussion

In all areas of science, good scientific practice is important. This has received more and more attention in recent years, particularly in light of the problems with scientific reproducibility. While most researchers are aware of the problems with good scientific practice, not all of these problems are necessarily clear, and the specifics can be very complicated. Sequencing-based microbiome studies have been published and accepted for a long time without proper controls. Despite the fact that more scientists are now realizing the need for controls, the complexity of the field makes this difficult. In microbiome studies, the inability to correctly interpret data from controls is another concern. One of the main issues with S-based categorization in the microbiological field is contamination, especially when only very small quantities of bacteria or compounds made from bacteria are present. In this situation, the presence of environmental pollutants, laboratory reagents, and individuals participating in sample preparation could have a significant impact on the findings of the investigations and lead to incorrect conclusions. It is interesting to note that longitudinal studies like Turner et al. Due to the possibility that different batches of the same extraction kits could identify different contaminants, these examples unmistakably demonstrate that microbiological investigations should always include several negative controls in order to account for contaminants and produce reliable results.

It is now clear that the systemic circulation of various populations contains extremely diverse microbial communities, and those both quantitative and compositional changes in the circulating microbiota may contribute to the onset and progression of cardiometabolic disease. However, there are still a lot of important questions about the nature of the circulating microbiota, such as where they come from, how they play a role in pathophysiology, how they can be found in different blood fractions, and how to tell them apart from potential contamination. These questions need to be answered in more in-depth basic, clinical, and population-based research in the future. Perhaps the time has come to go beyond the "gut feeling" and rigorously incorporate the potential pathophysiological insights gained from the circulating microbiota toward the development of novel biomarkers for diagnosis and prognosis, particularly in personalized therapeutic approaches to premature morbidity and mortality in cardiometabolic disease where patterns are emerging in the ongoing quest to improve the outcomes of patients with cardiometabolic disease [5].

Conclusion

In this review, we have chosen a few of the most recent cross-sectional studies of human cohorts that have made it possible to elucidate the changes in the blood microbiome that are associated with cardiovascular disease and other diseases. These investigations have provided new insights into ecological differences (dysbiosis), biological entities (new species), genebased variations (biomarkers) related to illness diagnosis, and the effects of current treatment therapies on the circulating microbiota. The significance of the blood microbiome in the emergence of cardiovascular and other disorders has been firmly established by numerous studies. Despite the complexity of the microbiome and the confounding effects of host genetics, nutrition, medical co-morbidities, and other lifestyle factors, the "omics"-based techniques are providing new insights into disease pathogenesis. Certain may lead to the development of treatments that could be used to treat and prevent metabolic diseases. Because many of these microbes are still difficult to cultivate, it is challenging to properly comprehend their role in disease development and prevention and to use this information to apply microbiome research to medicine. To successfully supplement and convey the headways being made by microbial genomics, there is an earnest requirement for resurgence of premium in microbial science. Bringing metagenomic data to life in the form of viable microbes will support the ability to provide individualized therapeutic and/or preventative interventions, such as "next generation," logically assembled microbial consortia and probiotics, as well as dietary changes for reestablishing a gut microbiota that promotes and sustains health.

Acknowledgement

None.

Conflict of Interest

None.

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