Testing the efficacy of dietary butyrate in ameliorating ataxic symptoms in Friedreich’s ataxia mouse models

Together with degeneration in the brain and spinal cord, FRDA patients frequently develop metabolic complications that culminate in heart disease and type 2 diabetes, which significantly aggravate FRDA progression. A direct link has been discovered in recent years between the gut and the brain, and alteration of the composition of the microbial gut population is associated with several neurodegenerative diseases. In this project, by using mouse models of FRDA, Dr. Lettieri-Barbato and his team will investigate whether the gut microbiome is altered in FRDA with a particular focus on bacteria producing short-chain fatty acids, including butyrate, as these molecules possess both a neuroprotective and anti-diabetic function. FRDA mice will be treated with a diet rich in butyrate, and the effect on motor function and molecular hallmarks of the disease will be analyzed in the cerebellum at single cell level. If butyrate demonstrates efficacy in mitigating the neuromotor symptoms and molecular deregulation identified in the cerebellum of FRDA mouse models, translation from bench to bedside could be highly feasible as this physiologically produced molecule has been shown to be safe in humans.