Actividad Investigadora
La interacción entre el microbioma intestinal y miR30c: potencial estrategia terapéutica para el dolor neuropático (GutmiRNApain). Gut microbiome-miR30c cross-talk: a potential novel.
Datos básicos
- Código del Financiador:
- INNVAL23/12
- Año Inicial:
- 2023
- Año final:
- 2026
Objetivos del proyecto
Neuropathic pain in animals: The subjects of the study will be mice and/or rats of both sexes. 1. To determine the alterations in the gut microbiome composition after chemotherapy-induced nerve injury and its association with the severity of the allodynia developed. 2. To assess the impact of gut microbiota in the levels of expression of mir30c-5p in circulating fluids (plasma and CSF), structures of the nervous system (DSH and DRG), and on nociception- related behaviors in rats subjected to chemotherapy-induced peripheral neuropathy 3. To evaluate the influence of the gut microbiome in the antiallodynic effect of mir-30c inhibitor in a model of peripheral neuropathy in rats. We hypothesize that the treatment with miR-30c-5p-inhibitor will prevent gut microbiome dysbiosis after nerve injury, which might contribute to the preventive and curative properties of miR-30c inhibitor against neuropathic pain. We will use the following approach: • To evaluate the consequences of miR-30c loss-of-function in the nervous system on the gut microbiota composition in rats subjected to peripheral neuropathy. • To assess whether the gut microbiota from rats treated with miR-30c inhibitor and subjected to nerve injury may confer protection against the development of neuropathic pain or reverse the allodynia established after nerve injury in a susceptible animal • To unravel sexually dimorphic responses that miR-30c inhibitor-based therapeutics may eventually elicit 4. To unravel whether the gut microbiome is involved in the antiallodynic effect of TGF-ß in chemotherapy-induced peripheral neuropathy in mice. Painful peripheral neuropathy in patients 5. To assess the potential clinical value of the composition of the gut microbiome as a biomarker with diagnostic, prognostic, and or patient stratification in chemotherapy-induced peripheral neuropathy. • Recruitment, clinical assessment of pain, and obtention of plasma and fecal samples from patients suffering from colorectal cancer subjected to chemotherapy with oxaliplatin. Samples will be obtained before and 1, 2, 3, 6, and 12 months after treatment. • 16s RNA gene sequencing of fecal samples • Determination of expression levels of miR-30c in plasma (qPCR). • Evaluation of possible interactions between circulating miR-30c levels and gut microbiota composition (logistic regression analysis).
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