VITA GutMicrobiome: New Approaches to Understand and Treat Cardiovascular Diseases
Cardiovascular diseases (CVDs) are the leading cause of death globally, claiming 17.9 million lives annually according to the WHO[1]. CVDs include coronary heart disease, cerebrovascular disease, rheumatic heart disease, and other heart and blood vessel disorders. Major risk factors include hypertension, high cholesterol, smoking, diabetes, and obesity.
In the past decade, the gut microbiome—the complex environment of our intestines—has emerged as another significant factor in CVD pathogenesis. This microbial environment both responds to and influences cardiovascular risk factors, producing components that can impact the host's cardiovascular health in diverse ways (Figure 1).
Figure 1: Gut dysbiosis is linked to endogenous and exogenous risk factors, the latter related to several systemic inflammatory and metabolic conditions [2].
The Association of the Gut Microbiota Composition and CVDs
The pivotal connection between the gut microbiome and cardiovascular disease (CVD) has been a focus of extensive research efforts. A recent study demonstrated that an elevated abundance of Streptococcus spp and other species typically found in the oral cavity is associated with coronary atherosclerosis and systemic inflammation markers (Figure 2)[3].
Figure 2: Associations between coronary artery calcium score–associated gut species and alternate measurements of atherosclerosis and markers of inflammation and infection [3].
Another study reported decreased diversity of gut microbiota, along with reduced synthesis of short-chain fatty acids (SCFAs) for individuals with ischemic heart disease. This trend becomes more pronounced as the disease progresses (Figure 3)[4]. Similar disruptions in the gut microbiota have also been noted in patients with heart failure, characterized by decreased diversity and a lower abundance of beneficial bacteria capable of producing SCFAs [5].
Figure 3: Alterations of gut microbiota and metabolome features along the natural history of IHD [4].
Blood pressure, a critical factor in the development and progression of CVDs, is associated with the gut microbiota diversity. Reduced blood pressure variability is linked to a high diversity of gut microbiota, specific microbial metabolites, and the presence of certrain species such as Alistipes finegoldii and Lactobacillus. Conversely, higher blood pressure variability is associated with the presence of genera such as Clostridium and Prevotella (Figure 4) [6].
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Figure 4: Differential abundance analysis of specific bacterial taxa for blood pressure[6].
Gut Microbiota‘s Metabolites and Components: Drivers of Cardiovascular Disease
The human intestine presents one of the largest interfaces with the external environment. Dysbiosis, the imbalance in gut microbiota, is a key factor significantly influencing gut barrier function. This can lead to the translocation of microorganisms or their products into the systemic circulation.
Lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, promotes a pro-inflammatory state by activating various immune receptors on cells such as leukocytes and endothelial cells once it enters the human circulatory system. This inflammatory response can contribute to thrombosis and the formation of atherosclerotic plaques, thereby increasing the risk of CVDs [7].
In addition to LPS, other microbial metabolites other microbial metabolites, including trimethylamine N-oxide (TMAO)/trimethylamine (TMA), short-chain fatty acids (SCFAs), and bile acids influence the risk and progression of CVDs. Researchers identified the pathogenic role of the bacterial metabolite TMAO[8]. In addition, bacteria produce N,N,N-trimethyl-5-aminovaleric acid (TMAVA), which disrupts cardiac energy metabolism, inhibits fatty acid oxidation, and can lead to myocardial lipid accumulation, exacerbating cardiac dysfunction (Figure 5) (Figure 5) [9].
Figure 5: TMAVA exacerbates myocardial hypertrophy and dysfunction[9].
As a potentially modifiable factor, the gut microbiota presents immense potential for preventive and interventional strategies. Recent research has revealed that the gut microbiota metabolite kynurenine (Kyn) is significantly elevated in children and mouse models with pressure-overloaded left ventricular (poLV) diseases. Single-nucleus RNA sequencing demonstrated that Kyn activates human aryl hydrocarbon receptors (AHRs), leading to the upregulation of genes associated with hypertrophy and fibrosis in cardiomyocytes and cardiac fibroblasts. Notably, supplementation with selected microbes has been shown to reduce Kyn levels and alleviate ventricular remodeling (Figure 6) [10].
Figure 6: Probiotics reconstructs gut microbiota of nAAC mice and reduces plasma Kyn [10].
Furthermore, a Ganoderma meroterpene derivative (GMD) has been shown to mitigate obesity-associated atherosclerosis in mice by altering the gut microbiota composition, notably by increasing the abundance of Parabacteroides merdae. This bacterium enhances branched-chain amino acid (BCAA) catabolism, thereby contributing to the reduction of atherosclerotic lesions [11].
Beyond Bulk: Revolutionizing Gut Microbiota Studies with VITA GutMicrobiome
Understanding the profound connections between the gut microbiota and their products and cardiovascular health requires detailed insights exceeding the capacites of conventional methods. While bulk 16S rRNA sequencing and metaOmics have provided foundational insights into microbial diversity and function, they lack the granularity needed to dissect the specific roles of individual bacteria within the complex gut microbiota ecosystem.
In November 2023, M20 Genomics launched an innovative tool to address these challenges: VITA GutMicrobiome High-Throughput Single-Bacterium Transcriptome (Figure 7). This cutting-edge technology marks a significant advancement in the field, enabling precise single-bacterium transcriptome profiling directly from gut microbiome samples.
Figure 7: VITA GutMicrobiome solution
VITA GutMicrobiome utilizes random primers to capture RNA and precisely barcodes individual bacteria, offering unprecedented insights into the interplay between gut microbiota and cardiovascular health. This approach enhances precision in quantifying relative bacterial abundance and can identify rare microbial populations that conventional methods might overlook. The comprehensive transcriptome profiles allow detailed insights gene expression profiles that unveil the microbial metabolic activities.
Beyond its scientific implications, VITA GutMicrobiome holds promise for translating discoveries into clinical applications. This technology has the potential to pioneer diagnostic approaches and personalized treatments tailored to individual gut microbiota profiles. Moreover, the detailed characterization of microbial strains presents a powerful tool to accelerate the development of live biotherapeutics.
Join us in shaping the future of gut microbiome research with VITA GutMicrobiome. Together, let's drive scientific discoveries and develop effective strategies to diagnose, treat, and prevent cardiovascular diseases!
References:
[1] https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1 (2024-06-08)
[2] Nesci, A., Carnuccio, C., Ruggieri, V., D'Alessandro, A., Di Giorgio, A., Santoro, L., Gasbarrini, A., Santoliquido, A., & Ponziani, F. R. (2023). Gut Microbiota and Cardiovascular Disease: Evidence on the Metabolic and Inflammatory Background of a Complex Relationship. International journal of molecular sciences, 24(10),
[3] Sayols-Baixeras, S., Dekkers, K. F., Baldanzi, G., et, al. (2023). Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort. Circulation, 148(6), 459-472.
[4] Fromentin, S., Forslund, S. K., Chechi, K., et, al. (2022). Microbiome and metabolome features of the cardiometabolic disease spectrum. Nature medicine, 28(2), 303-314.
[5] Beale, A. L., O'Donnell, J. A., Nakai, M. E., et, al. (2021). The Gut Microbiome of Heart Failure With Preserved Ejection Fraction. Journal of the American Heart Association, 10(13), e020654.
[6] Dinakis, E., Nakai, M., Gill, P., et, al. (2022). Association Between the Gut Microbiome and Their Metabolites With Human Blood Pressure Variability. Hypertension, 79(8), 1690–1701.
[7] Violi, F., Cammisotto, V., Bartimoccia, S., et, al. (2023). Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease. Nature reviews. Cardiology, 20(1), 24–37.
[8] Wang, Z., Klipfell, E., Bennett, B. J., et, al. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57–63.
[9] Zhao, M., Wei, H., Li, C., et, al. (2022). Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy. Nature communications, 13(1), 1757.
[10] Shi, B., Zhang, X., Song, Z.,et, al. (2023). Targeting gut microbiota-derived kynurenine to predict and protect the remodeling of the pressure-overloaded young heart. Science advances, 9(28), eadg7417.
[11] Qiao, S., Liu, C., Sun, L., et, al. (2022). Gut Parabacteroides merdae protects against cardiovascular damage by enhancing branched-chain amino acid catabolism. Nature metabolism, 4(10), 1271–1286.
