دورية أكاديمية
Combining fecal 16 S rRNA sequencing and spinal cord metabolomics analysis to explain the modulatory effect of PPARα on neuropathic pain.
| العنوان: | Combining fecal 16 S rRNA sequencing and spinal cord metabolomics analysis to explain the modulatory effect of PPARα on neuropathic pain. |
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| المؤلفون: | Wu ZJ; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin 300052, China., Zhao YY; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin 300052, China., Hao SJ; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin 300052, China., Dong BB; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin 300052, China., Zheng YX; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin 300052, China., Liu B; Department of Critical Care Medicine, General Hospital of Tianjin Medical University, Tianjin 300052, China; Center for Critical Care Medicine, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300020, China. Electronic address: liubin78@163.com., Li J; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin 300052, China. Electronic address: xtjing@163.com. |
| المصدر: | Brain research bulletin [Brain Res Bull] 2024 Jun 01; Vol. 211, pp. 110943. Date of Electronic Publication: 2024 Apr 12. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 7605818 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2747 (Electronic) Linking ISSN: 03619230 NLM ISO Abbreviation: Brain Res Bull Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Elsevier Science Original Publication: Phoenix, N. Y. ANKHO International Inc. |
| مواضيع طبية MeSH: | Gastrointestinal Microbiome*/drug effects , Gastrointestinal Microbiome*/physiology , Metabolomics* , Neuralgia*/metabolism , Neuralgia*/drug therapy , Neuralgia*/microbiology , PPAR alpha*/metabolism , RNA, Ribosomal, 16S*/genetics , Spinal Cord*/metabolism , Spinal Cord*/drug effects, Animals ; Male ; Mice ; Feces/microbiology ; Mice, Inbred C57BL ; Microglia/metabolism ; Microglia/drug effects ; Oxazoles ; Tyrosine/analogs & derivatives |
| مستخلص: | Background: Existing evidence suggests that the composition of the gut microbiota is associated with neuropathic pain (NP), but the mechanistic link is elusive. Peroxisome proliferator-activated receptor α (PPARα) has been shown to be a pharmacological target for the treatment of metabolic disorders, and its expression is also involved in inflammatory regulation. The aim of this study was to investigate the important modulatory effects of PPARα on gut microbiota and spinal cord metabolites in mice subjected to chronic constriction injury. Methods: We analyzed fecal microbiota and spinal cord metabolic alterations in mice from the sham, CCI, GW7647 (PPARα agonist) and GW6471 (PPARα antagonist) groups by 16 S rRNA amplicon sequencing and untargeted metabolomics analysis. On this basis, the intestinal microbiota and metabolites that were significantly altered between treatment groups were analyzed in a combined multiomics analysis. We also investigated the effect of PPARα on the polarization fractionation of spinal microglia. Results: PPARα agonist significantly reduce paw withdrawal threshold and paw withdrawal thermal latency, while PPARα antagonist significantly increase paw withdrawal threshold and paw withdrawal thermal latency. 16 S rRNA gene sequencing showed that intraperitoneal injection of GW7647 or GW6471 significantly altered the abundance, homogeneity and composition of the gut microbiome. Analysis of the spinal cord metabolome showed that the levels of spinal cord metabolites were shifted after exposure to GW7647 or GW6471. Alterations in the composition of gut microbiota were significantly associated with the abundance of various spinal cord metabolites. The abundance of Licheniformes showed a significant positive correlation with nicotinamide, benzimidazole, eicosanoids, and pyridine abundance. Immunofluorescence results showed that intraperitoneal injection of GW7647 or GW6471 altered microglial activation and polarization levels. Conclusion: Our study shows that PPARα can promote M2-type microglia polarization, as well as alter gut microbiota and metabolites in CCI mice. This study enhances our understanding of the mechanism of PPARα in the treatment of neuropathic pain. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Gut microbiota; Neuropathic pain; PPARα; Spinal cord metabolism |
| المشرفين على المادة: | 0 (GW 6471) 0 (Ppara protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240413 Date Completed: 20240427 Latest Revision: 20240522 |
| رمز التحديث: | 20240522 |
| DOI: | 10.1016/j.brainresbull.2024.110943 |
| PMID: | 38614408 |
| قاعدة البيانات: | MEDLINE |
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