59: The Gut Virome Modulates Neuropathic Pain in Diabetes via the TLR4/C/EBPβ Signaling Pathway.

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Omics (Proteomics/Metabolomics/Transcriptomics/Genomics), Assessment and Measurement of Pain/Nociception

Background and Aims: Diabetic peripheral neuropathic pain (DPNP) is a prevalent and debilitating complication of diabetes that diminishes patients' quality of life. While the gut microbiome's role in DPNP is increasingly recognized, the specific mechanisms, including those involving gut viruses, are not fully understood.

Methods: We established a DPNP mouse model through intraperitoneal streptozotocin injection. We administered antiviral and antibiotic treatments and assessed their effects on mechanical allodynia. We analyzed changes in gut and serum lipopolysaccharide (LPS) levels, gut barrier function, neuroinflammation in the hippocampus and spinal cord, and the activity of C/EBPβ and TLR4 pathways using appropriate statistical tests.

Results: Both treatments significantly alleviated mechanical allodynia, with antibiotics showing a more pronounced effect by reducing LPS-producing bacteria. Antiviral therapy increased the lytic activity against these bacteria. Decreased LPS levels led to improved gut barrier integrity, reduced neuroinflammation, and alleviated DPNP symptoms. The inhibition of neuroinflammation was associated with the suppression of the C/EBPβ and TLR4 pathways.

Conclusions: Our study highlights the significant role of the gut microbiome, including both bacterial and viral components, in DPNP pathogenesis. Modulating the gut microbiome by targeting LPS-producing bacteria and regulating the C/EBPβ and TLR4 pathways could offer novel therapeutic approaches for DPNP management. This research provides a foundation for developing future treatment strategies that consider the interplay between gut microbiota and neuropathic pain.

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Presenting Author: Keyang Duan
Submitting Author: Ke yang Duan

Senior Author: Tao Sun

IASP 2026 Global Year theme of Neuropathic Pain: Yes