Gut instinct: microbiome as a modifiable target in the management of neurologic symptoms in myoclonic epilepsy with ragged-red fibers (MERRF)

Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial disorder primarily driven by mutations in mitochondrial DNA, particularly the m.8344A>G variant in MT-TK, and is characterized by epilepsy, myoclonus, ataxia, and other multisystemic features. With no curative therapy, recent attention has turned to the gut microbiome as a modifiable factor influencing neurologic symptoms in mitochondrial diseases. Dysbiosis-induced by antibiotics, diet, or preservatives-has been linked to altered microbial metabolites such as short-chain fatty acids and indoxyl sulfate, which may exacerbate neurological dysfunction. Preliminary clinical trials and preclinical studies suggest that probiotics and dietary interventions can modestly improve disease burden and symptoms such as constipation. However, significant challenges remain, including lack of standardization in analytical protocols, heterogeneous host-microbiota responses, and inadequate patient stratification. To fully realize the therapeutic potential of microbiome-based approaches in MERRF, coordinated multicenter trials, clear regulatory guidelines, and machine learning-enhanced stratification will be essential.