SCFAs’ pleiotropic role in pathogenesis and salutogenesis: mechanisms in exacerbation and regulation of inflammation and fibrosis from gut to host

B and reactive oxygen species pathways (e.g. succinate), potentially resulting in vascular inflammation. While SCFAs typically suppress inflammation through histone deacetylase inhibition and immune regulation, pro-inflammatory roles emerge in specific settings. Within immune compartments, SCFAs exhibit cell-specific effects, from priming cell-driven pro-inflammatory roles in one type of immune cell to suppression of inflammatory mediators in others. Moreover, SCFAs can lead to fibrotic remodelling, an intensified form of inflammation in both intestinal and distant tissues. This review aims to demonstrate the complex biphasic bridge between aggravation and resolution influenced by factors such as cell type, study methodologies, receptors, dose dependency, age, metabolic changes and inherent properties and concludes with the significance of particular and accurate research approaches to mimic the true environment and observe SCFA effects employing humanized mice, gut-on-chip systems and organoids for more precise and relevant results.