Role of Short Chain Fatty Acids in Epilepsy and Potential Benefits of Probiotics and Prebiotics: Targeting “Health” of Epileptic Patients

The WHO’s definition of health transcends the mere absence of disease, emphasizing physical, mental, and social well-being. As this perspective is being increasingly applied to the management of chronic diseases, research on gut microbiota (GM) is surging, with a focus on its potential for persistent and noninvasive dietary therapeutics. In patients with epilepsy (PWE), a chronic lack of seizure control along with often neglected psychiatric comorbidities greatly disrupt the quality of life. Evidence shows that GM-derived short chain fatty acids (SCFAs) may impact seizure susceptibility through modulating (1) excitatory/inhibitory neurotransmitters, (2) oxidative stress and neuroinflammation, and (3) psychosocial stress. These functions are also connected to shared pathologies of epilepsy and its two most common psychiatric consequences: depression and anxiety. As the enhancement of SCFA production is enabled through direct administration, as well as probiotics and prebiotics, related dietary treatments may exert antiseizure effects. This paper explores the potential roles of SCFAs in the context of seizure control and its mental comorbidities, while analyzing existing studies on the effects of pro/prebiotics on epilepsy. Based on currently available data, this study aims to interpret the role of SCFAs in epileptic treatment, extending beyond the absence of seizures to target the health of PWE.