Ginger Polyphenols Reverse Molecular Signature of Amygdala Neuroimmune Signaling and Modulate Microbiome in Male Rats with Neuropathic Pain: Evidence for Microbiota–Gut–Brain Axis
Chwan-Li Shen,
Julianna Maria Santos,
Moamen M. Elmassry,
Viren Bhakta,
Zarek Driver,
Guangchen Ji,
Vadim Yakhnitsa,
Takaki Kiritoshi,
Jacob Lovett,
Abdul Naji Hamood,
Shengmin Sang,
Volker Neugebauer
Affiliations
Chwan-Li Shen
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Julianna Maria Santos
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Moamen M. Elmassry
Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA
Viren Bhakta
Department of Biology, Texas Tech University, Lubbock, TX 79401, USA
Zarek Driver
Department of Biochemistry, Texas Tech University, Lubbock, TX 79401, USA
Guangchen Ji
Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Vadim Yakhnitsa
Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Takaki Kiritoshi
Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Jacob Lovett
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Abdul Naji Hamood
Department of Microbiology and Infectious Disease, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Shengmin Sang
Laboratory for Functional Foods and Human Health, Center for Excellence in Post Harvest Technologies, North Carolina A&T State University, North Carolina Research Campus, Kannapolis, NC 28081, USA
Volker Neugebauer
Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Emerging evidence shows that the gut microbiota plays an important role in neuropathic pain (NP) via the gut–brain axis. Male rats were divided into sham, spinal nerve ligation (SNL), SNL + 200 mg GEG/kg BW (GEG200), and SNL + 600 mg GEG/kg BW (GEG600) for 5 weeks. The dosages of 200 and 600 mg GEG/kg BW for rats correspond to 45 g and 135 g raw ginger for human daily consumption, respectively. Both GEG groups mitigated SNL-induced NP behavior. GEG-supplemented animals had a decreased abundance of Rikenella, Muribaculaceae, Clostridia UCG-014, Mucispirillum schaedleri, RF39, Acetatifactor, and Clostridia UCG-009, while they had an increased abundance of Flavonifactor, Hungatella, Anaerofustis stercorihominis, and Clostridium innocuum group. Relative to sham rats, Fos and Gadd45g genes were upregulated, while Igf1, Ccl2, Hadc2, Rtn4rl1, Nfkb2, Gpr84, Pik3cg, and Abcc8 genes were downregulated in SNL rats. Compared to the SNL group, the GEG200 group and GEG600 group had increases/decreases in 16 (10/6) genes and 11 (1/10) genes, respectively. GEG downregulated Fos and Gadd45g genes and upregulated Hdac2 genes in the amygdala. In summary, GEG alleviates NP by modulating the gut microbiome and reversing a molecular neuroimmune signature.
