Metabolomics and Gut Microbiota in Elderly Patients with Diabetic Peripheral Neuropathy and Sarcopenia

Abstract

Background: Diabetes peripheral neuropathy (DPN) is closely related to the occurrence and development of sarcopenia. However, the relevant early biological metabolites and their pathophysiological mechanism is unclear. Aim: To explore the underlying mechanisms of Diabetic Peripheral Neuropathy with Sarcopenia (DPNS) by integrating metabolomics and 16S rRNA sequencing. Methods: A total of 151 diabetic neuropathy patients were enrolled in the study. Untargeted metabolomics was performed using ultra-high-performance liquid. Chromatography-mass spectrometry, andgut microbiota was assessed through 16S rRNA sequencing. Differential metabolites and microbial taxa were identified, and theirassociations were explored using correlation analysis. Results: A total of 376 differential metabolites were identified. Compared with the DPN group, the contents of glycerophosphocholine(GPC), taurine, and succinic acid in the DPNS group were significantly decreased, while that of 2-amino-1-methyl-6-phenylimidazo(4, 5-b)pyridine(PhIP), Sphingosine were increased. Gutmicrobiota analysis revealed reduced diversity in DPNS, with decreased beneficial genera (Faecalibacterium, Bacteroides) and increased pathogenic taxa (Streptococcus). Additionally, KEGG enrichment analysis showed that the mammalian target of necroptosis, sphingolipid metabolism, the mTOR signaling pathway, ABC transporters, and bile secretion pathways are closely related to DPNS. Conclusion: We systematically explored the biomarkers and potential therapeutic targets in the patients with DPNS, which may provide new insights that may advance the treatment of sarcopenia.