Introduction
The keys to the immune system: Short Chain Fatty Acids (SCFAs) and their impact on allergic diseases
Short Chain Fatty Acids (SCFAs) are fermented components of the diet that play a crucial role in the regulation of immune responses, promotion of colonic health and mast cell-mediated disease suppression. However, to date, the effects of SCFAs on human mast cell function, as well as the underlying mechanisms, have remained largely unknown. Here, we explore the effects of SCFAs, in particular butyrate, on mast cell-mediated pathology and activation of human mast cells, unravelling the molecular mechanisms involved.
Method
Ex Vivo Model and Human Barley Cells: The Key to Unravelling the Effects of Butyrate
To assess the effects of butyrate on allergic airway contraction, we used precision-cut lung slices (PCLS) from guinea pigs exposed to allergens. We also co-cultured human and murine mast cells with SCFAs and assessed degranulation after IgE-mediated or non-IgE-mediated stimulation. Our experiments included the use of knockout mice, small molecule inhibitors/agonists and genomic assays.
Results
Butyrate: an Epigenetic Regulator of Barley Cell Activation
Our results revealed that butyrate treatment inhibited allergen-induced histamine release and airway contraction in guinea pig PCLS. In addition, both propionate and butyrate, but not acetate, inhibited IgE-mediated and non-IgE-mediated degranulation of human and murine mast cells in a concentration-dependent manner. These effects were associated with inhibition of histone deacetylases (HDACs). Transcriptome analyses revealed butyrate-induced downregulation of the tyrosine kinases BTK, SYK and LAT, crucial transducers of FcεRI-mediated signals essential for mast cell activation. Epigenome analyses indicated that butyrate redistributed global histone acetylation in human barley cells, including a significant decrease in acetylation in the BTK, SYK and LAT promoter regions.
Conclusion
Butyrate as a Potential Ally in the Fight Against Allergic Diseases
The known health benefits of SCFAs in allergic diseases may be explained, at least in part, by epigenetic suppression of human mast cell activation. These findings could open up new therapeutic perspectives in the field of allergic diseases and the regulation of mast cell activation.
This study sheds light on the relationship between SCFAs and the activation of mast cells, revealing a new epigenetic pathway that can be exploited in the treatment of allergic diseases. Understanding how butyrate and other SCFAs affect mast cells and their activation offers new perspectives for the development of more effective and less invasive therapies in the treatment of allergic diseases and related disorders. Ref.: https://onlinelibrary.wiley.com/doi/10.1111/all.14254
