Changes of intestinal microbiome and its relationship with painful diabetic neuropathy in rats.

Abstract

Objective: To analyze the gut bacterial microbiome in rats with painful diabetic neuropathy (PDN) compared to normal rats.

Methods: Type 2 diabetes was induced in rats via a high-fat and high-sugar diet combined with a low dose of streptozotocin. Glucose metabolism and insulin sensitivity were evaluated using intraperitoneal glucose tolerance tests and insulin tolerance tests. The progression of peripheral neuropathy was assessed using the mechanical withdrawal threshold and thermal withdrawal latency. Histopathological analysis of rat colon tissues was performed using hematoxylin-eosin staining to observe morphological changes. The expression levels of pro-inflammatory cytokines TNF-α and IL-1β in spinal cord tissues were measured using enzyme-linked immunosorbent assay (ELISA). Fecal samples were then collected for metagenomic sequencing and analysis.

Result: Behavioral tests revealed reduced mechanical withdrawal threshold and thermal withdrawal latency in PDN rats. Histological analysis showed significant colonic mucosal damage and inflammatory cell infiltration, suggesting impaired intestinal barrier function. Elevated TNF-α and IL-1β levels in spinal cord tissues further highlight peripheral inflammation's role in PDN. Sequencing analysis revealed significant differences in gut microbiota composition between PDN and control rats, with altered Bacillota/Bacteroidota ratios and increased Lactobacillus abundance. Functional annotation analysis, based on the KEGG, EggNOG, and CAZy databases, indicated significant enrichment of metabolic pathways related to carbohydrate and amino acid metabolism, energy metabolism, and cell structure biogenesis in PDN rats. Cluster analysis identified higher functional clustering in Metabolism and Genetic Information Processing pathways in PDN rats.

Conclusion: This study demonstrates that PDN leads to altered gut microbiota composition, disrupted metabolic pathways, and increased inflammation, contributing to the pathological progression of diabetic neuropathy. This study provides new insights into the interplay between gut microbiota and diabetic neuropathy, offering potential avenues for therapeutic interventions targeting microbiome and metabolism.