The effect of short chain fatty acids on ethanol toxicity in SH-SY5Y cells 4163

Abstract Description Ethanol toxicity poses significant risks to liver function and the central nervous system (CNS), contributing to inflammation and neuronal damage. Chronic ethanol consumption induces oxidative stress and activates glial cells, exacerbating neurodegenerative diseases (NDDs) such as Alzheimer’s disease. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are metabolites produced by gut microbiota from dietary fibers and have been shown to reduce neuroinflammation, support blood-brain barrier integrity, and modulate immune responses. Butyrate, in particular, inhibits microglial activation and reduces neuroinflammation. However, excessive alcohol consumption reduces SCFA-producing gut microbes, which may worsen inflammation and neurodegeneration. Preliminary results from this study show that ethanol treatment alters the expression of immune receptors, increasing TLR8 and FFAR4 while decreasing GPR84. SCFA treatment reversed some of these changes, and SCFAs demonstrated neuroprotective effects in a dose-dependent manner. These findings suggest that while SCFAs can alleviate ethanol-induced inflammation, they are not a standalone solution. A combined approach of reducing alcohol intake and maintaining a fiber-rich diet to promote SCFA production is essential for mitigating ethanol’s toxic effects. This research highlights the potential for targeting SCFA pathways and immune receptors to develop novel therapeutic strategies for NDDs. Topic Categories Neuroimmunology (NEUR)