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. ### Competing Interest Statement Liping Zhao is a co-founder of Notitia Biotechnologies Company. ### Clinical Trial ChiCTR1800017257 ### Funding Statement This work was supported by the following funding supports: National Natural Science Foundation of China (81970705, 81871091, and 31922003). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee of Henan Provincial People's Hospital gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are available from the corresponding author upon request. Metagenomic sequence data have been submitted in DDBJ () with accessions number DRA009982. Amplicon sequence data have been submitted in NCBI SRA () with accessions number SRP379656, SRP278004 and SRP272175.