Polyglutamine　(polyQ)-mediated　mitochondria　damage　is　one　of　the　prime　causes　of　polyQ　toxicity,　which　leads　to　the　loss　of　neurons　and　the　injury　of　non-neuronal　cells.　With　the　discovery　of　the　crucial　role　of　the　gut-brain　axis　and　gut　microbes　in　neurological　diseases,　the　relationship　between　visceral　damage　and　neurological　disorders　has　also　received　extensive　attention.　This　study　successfully　simulated　the　polyQ　mitochondrial　damage　model　by　expressing　78　or　84　polyglutamine-containing　Ataxin3　proteins　in　Drosophila　intestinal　enterocytes.　In　vivo,　polyQ　expression　can　reduce　mitochondrial　membrane　potential,　mitochondrial　DNA　damage,　abnormal　mitochondrial　morphology,　and　loose　mitochondrial　cristae.　Expression　profiles　evaluated　by　RNA-seq　showed　that　mitochondrial　structural　genes　and　functional　genes　(oxidative　phosphorylation　and　tricarboxylic　acid　cycle-related)　were　significantly　down-regulated.　More　importantly,　Bioinformatic　analyses　demonstrated　that　pathological　polyQ　expression　induced　vitamin　B6　metabolic　pathways　abnormality.　Active　vitamin　B6　participates　in　hundreds　of　enzymatic　reactions　and　is　very　important　for　maintaining　mitochondria?s　activities.　In　the　SCA3　Drosophila　model,　Vitamin　B6　supplementation　significantly　suppressed　ECs　mitochondria　damage　in　guts　and　inhibited　cellular　polyQ　aggregates　in　fat　bodies,　indicating　a　promising　therapeutic　strategy　for　the　treatment　of　polyQ.　Taken　together,　our　results　reveal　a　crucial　role　for　the　Vitamin　B6-mediated　mitochondrial　protection　in　polyQ-induced　cellular　toxicity,　which　provides　strong　evidence　for　this　process　as　a　drug　target　in　polyQ　diseases　treatment.