The anti-inflammatory effects of short chain fatty acids on human endothelial and lung epithelial cells - Ferment your fruits and vegetables to battle NCDs!

Abstract

Our body is attacked continuously by a variety of dangerous signals and an effective balanced immune system is essential to recognize and respond to these. Unbalanced immune reactivity plays a key role in so-called non-communicable diseases (NCDs). The main types of NCDs are cardiovascular diseases, chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma and respiratory allergy, cancers and diabetes. The reasons for the increase in NCDs are multifactorial and include changes in lifestyle, diet, hygiene, microbiome, industrial technologies, infections, etc. Given the aim of WHO global health task force to decrease 25% in NCDs associated mortality before 2025, we need a better understanding of the underlying mechanisms of NCDs. Since chronic low-grade inflammation is a common feature of all NCDs, reducing the risk of inflammatory responses might be a promising approach regarding both prevention and treatment. Currently, one highly promising candidate to influence the immune system and manage inflammatory processes in a proper way is microbiome modulation. Microbiome modulation can be achieved via different approaches such as the addition of probiotics, prebiotics, synbiotics and postbiotics. Short chain fatty acids (SCFA), fermentation products of non-digestible dietary fibre by microbiota in the intestine, are recognized as an example of postbiotics and receive attention for their anti-inflammatory and immune modulatory properties. Endothelial cells are involved in maintaining homeostasis and can be activated by TNFα or endotoxins (LPS). Endothelial cell activation is a central component of the vascular inflammatory process that promotes the development of atherosclerosis. The airway epithelium is involved in the protection of the host against inhaled pathogens, allergens and other noxious substances. Epithelial cells are the first cells to interact with inhaled antigens and other harmful substances that can result in increased secretion of cytokines and recruitment of immune cells. Damage to epithelial cells causes barrier dysfunction, leading to a further increase in their permeability and the development of respiratory diseases. This thesis will mainly focus on the effects of SCFA (which regulate inflammatory responses in endothelial cells and modulate the epithelial barrier function in lung epithelial cells in certain NCDs) on cardiovascular diseases and chronic respiratory diseases. Meanwhile, SCFA are known to (1) activate G-protein coupled receptors (GPCRs, GPR41 and GPR43, also known as FFA3 and FFA2 receptors) and (2) inhibit histone deacetylases (HDACs) [25]. In this thesis, the effects of SCFA were investigated on isolated cells, in particular endothelial and epithelial cells and the mechanisms involved.