Abstract
PURPOSE: Diabetic peripheral neuropathy (DPN) is one of the most common complications of type 2 diabetes mellitus (T2DM). In recent years, it has been reported that the progression of DPN is associated with altered gut microbiota and serum metabolites. However, the alterations of the gut microbiota and interaction with metabolites are not well understood in DPN patients. Therefore, we compared the gut microbiota and fecal and serum metabolic profiles of DPN and comprehensively analyzed the potential mechanisms of DPN. METHODS: A total of 50 patients were divided into two groups: T2DM group without DPN (T2DM group) and T2DM group with DPN (DPN group). Fecal and serum samples of all patients were collected, and serum metabolites were determined by (1)H-Nuclear Magnetic Resonance ((1)H-NMR)-based metabolomics technique. The profile of gut microbiota was determined by 16S rRNA sequencing. Liquid chromatography-mass spectrometry (LC-MS) was used to detect fecal metabolites. The changes of gut microbiota, fecal and serum metabolites were compared and correlation analysis was conducted among them and clinical indicators, such as visual analogue scale (VAS) score, Toronto Clinical Scoring System (TCSS) score and electromyography indicators. RESULTS: Bacteria at the genus level in 8 and the species level in 13, and 28 fecal metabolites, and 5 serum metabolites were significantly altered in DPN patients. In particular, genus Faecalibacterium, species Collinsella_aerofaciens, fecal glycocholic acid and serum formate were significantly reduced in DPN, while genus Megamonas, fecal maleamic acid and serum uric acid (UA) were enriched. These changes are related to bile acid metabolism, amino acid metabolism, and mitochondrial dysfunction, as well as significantly correlated with VAS score, TCSS score and electromyography indicators. CONCLUSION: This study discovered the abnormal gut microbiota in DPN patients, with alterations in fecal and serum metabolism. It is speculated that the gut microbiota may lead to metabolic imbalance, accelerating the DPN progression. Multi-omics analysis was used to identify the possible mechanism of the gut microbiota-metabolism-mitochondrial axis in the progression of DPN, which may provide a potential therapeutic target for the diagnosis and treatment of DPN.