Non-animal derived nanovesicles from circular bioeconomy with symbiotic effects on malnutrition-related cardio vascular diseases – From farm to health

Gut microbiota and CVD

The healthy human intestine harbours several microorganisms, including bacteria of different families. When in homeostasis, the intestinal microbiota influences the host’s health. It affects host metabolism, the immune system and gut microbicide mechanisms, and maintains the intestinal barrier.

Changes in the composition of the intestinal microbiota (dysbiosis) contribute to the development of intestinal inflammation as well as extra-intestinal diseases associated with low-grade inflammation, including chronic inflammation, insulin resistance, type 2 diabetes mellitus (T2DM), CVD, and obesity (Hamjane et al., 2024).

Factors such as genetic predisposition, environmental elements, unhealthy high-calorie diets, and sedentary lifestyles are known contributors to obesity, T2DM, and CVD. However, evidence suggests an active role of the gut microbiome in modulating these diseases. Microbiome dysbiosis can influence gut or systemic immunity and inflammation by regulating intestinal barrier permeability or by triggering the innate immune system.

For instance, hyperglycemia can disrupt the intestinal barrier, allowing gram-negative bacterial products like lipopolysaccharides (LPS) to enter the systemic circulation, leading to local and systemic inflammation.

Studies have shown that microbiota are sensitive to the host’s diet composition and that microbiome diversity changes with animal vs. plant-based diets. The gut microbiota produces beneficial metabolites such as short-chain fatty acids (SCFA), protective against T2DM and CVD, and other favourable metabolites like esculin or anthocyanin. However, unfavourable metabolites such as propionate (linked to improved insulin sensitivity and weight) and trimethylamine (associated with increased low-density lipoprotein uptake and CVD) are also produced.

Additionally, gut microbes metabolize bile acids, enhancing insulin sensitivity and regulating lipid and glucose metabolism. Bile acids play a significant role in CVD, interacting with cardiac myocytes and affecting muscle contractility and electrical excitation (Thushara RM et al., 2016).

Current technologies

Microbiome supplementation alters the composition of the gut microbiome, resulting in effects on host health. Understanding host–microbiota interactions may yield novel therapeutic strategies, potentially transforming CVD prevention and treatment (Olas B., 2020).

Prebiotics, probiotics, and symbiotics represent treatment options for increasing beneficial microorganisms and reducing harmful ones.

• Prebiotics are beneficial consumable substances selectively utilized by microorganisms in the host. Inulin, lactulose, and fructooligosaccharides are the most widely known prebiotics. They confer health benefits including reduced inflammation and improved glucose homeostasis, and regulate metabolic disorders associated with obesity such as dyslipidemia, hypertension, and diabetes (Antony MA et al., 2023).
• Probiotics are live microorganisms benefiting the host, including Bifidobacterium and Lactobacillus. Their administration is a potential therapeutic approach for preventing and treating metabolic syndrome and impacting cardiovascular risk factors. They lower LDL-cholesterol, improve the LDL/HDL ratio, reduce blood pressure, inflammatory mediators, blood glucose levels, and body mass index.

Symbiotics are combinations of prebiotics and probiotics, consisting of live microorganisms and substances selectively utilized by the host microbiota to confer benefit. Benefits include reduced oxidative stress on intestinal cells, decreased inflammation, and maintenance of the gut barrier. Current symbiotics include well-studied probiotics such as Bifidobacterium and Lactobacillus, which ferment indigestible sugars.

Objectives of the proposed project:

1. Identify specific NVs from apple fruit, Lactobacillus sp., and Saccharomyces sp. with potential prebiotic properties.
2. Develop symbiotic formulations combining these NVs with a pool of beneficial microorganisms for targeted modulation of the intestinal flora.
3. Conduct comprehensive in vitro testing to assess the impact of the symbiotic formulations on cardiovascular cell systems.
4. Execute in vivo studies within an obese disease model to evaluate the efficacy of the formulated symbiotics in a physiological context.
5. Define the optimal combination of NVs and microorganisms through thorough analysis of in vitro and in vivo results.

Development of a product.