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Session: Nutritional Neuroscience: Nutrition and the Brain (Oral 4)

(OR04-03-23) Ginger Mitigates Pain in SNL-Treated Rats via Improving Gut Microbiome and Reversing Molecular Signature of Amygdala Neuroimmune Signaling: Microbiome-Brain-Axis

Saturday, July 22, 2023
2:54 PM – 3:06 PM ET
Location:  Commonwealth
Disclosure(s):
Chwan-Li Shen, PhD: American River Nutrition, LLC: Grant/Research Support (Ongoing)
Sabinsa Corporation: Grant/Research Support (Ongoing)
Shengmin Sang, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Gut microbiota may serve at the intersection between microbiome-gut-brain and neuroinflammation in the development of neuropathic pain (NP). We evaluated the effects of two dosages of gingerol-enriched ginger (GEG) on mechanical hypersensitivity, gut microbiome composition, and neuroinflammation signature genes expression in amygdala of NP animals.

Methods: 36 male rats were divided into: Sham, spinal nerve ligation (SNL group, pain model), SNL+200mg GEG/kg BW, p.o. (GEG200), and SNL+600mg GEG/kg BW, p.o. (GEG600) for 4 weeks. Hypersensitivity was assessed by von Frey test. Cecal fecal samples were collected for microbiota composition analysis using 16S rRNA gene sequencing. Neuroinflammation 770 gene expression profiling of amygdala was conducted using the nCounter® Neuroinflammation pathway panel (NanoString Technologies, Seattle, WA).

Results: Both GEG groups mitigated SNL-induced NP. The evenness and richness of gut microbiome species did not differ between Sham and SNL groups, whereas gut microbiome evenness and richness in both GEG groups were lower than in the SNL group. Several microbiome species were consistently altered by both GEG treatments. For example, Rikenella, Muribaculaceae, Clostridia UCG-014, Mucispirillum schaedleri, RF39, and Clostridia UCG-009 were decreased in GEG-supplemented rats vs. SNL rats. The following taxa were increased in GEG-supplemented animals vs. SNL: Flavonifactor, Hungatella, Anaerofustis stercorihominis, Acetatifactor, and Clostridium innocuum group. Among the 770 genes, 3 cell types (CD45+ peripheral immune cells, CNS oligodendrocytes, and CNS astrocytes) were identified in the amygdala. Relative to Sham rats, two genes (Fos and Gadd45g) were upregulated and 8 genes (Igf1, Ccl2, Hadc2, Rtn4rl1, Nfkb2, Gpr84, Pik3cg, and Abcc8) were downregulated in SNL rats. Compared to the SNL group, the GEG200 group and GG600 group induced changes in 16 genes (10 increased and 6 decreased) and 11 genes (1 increased and 10 decreased), respectively. Both GEG groups downregulated Fos and Gadd45g genes and upregulated Hdac2 gene than those in non-GEG rats.

Conclusions: GEG mitigates hypersensitivity in the rats with NP, in part, via improving gut microbiome composition and reversing molecular neuroimmune signature of the amygdala.

Funding Sources: USDA NIFA Grant no. 2021-67017-34026 (Shen/Neugebauer)