Gut microbiota modulates distal symmetric polyneuropathy in diabetic patients

The contribution of the gut microbiota to distal symmetric polyneuropathy (DSPN) in diabetic patients remains elusive. We found that the gut microbiota from DSPN patients induced more severe peripheral neuropathy in db/db mice. Gut microbiota from healthy donors significantly alleviated DSPN independent from glycaemic control in patients in a randomized, double-blind and placebo-controlled trial. The gut bacterial genomes correlated with Toronto Clinical Scoring System score were organized in two competing guilds. Increased Guild 1 that had higher capacity in butyrate production and decreased Guild 2 that harbored more genes in synthetic pathway of endotoxin were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched Guild 1 and suppressed Guild 2. Thus, the two competing guilds may mediate the causative role of the gut microbiota in DSPN and have the potential to be an effective target for treatment. Clinical Trial Registration ID #: ChiCTR1800017257.