Two Curcumin Extracts Modify Composition of Gut Microbiota, Tight Junction Protein, and Neuroinflammation in Rats With Neuropathic Pain: Microbiota-Gut-Brain Axis

OBJECTIVES: Emerging evidence suggests that gut microbiota may serve at the intersection between microbiome-gut-brain and neuroinflammation in the development of neuropathic pain (NP). This study evaluated the effects of curcumin C3 Complex® (CUR) and bisdemethoxy curcumin (CMO), on the composition of gut microbiota and intestinal permeability-/neuroinflammation-associated gene expression in animals with NP. METHODS: 23 male rats were randomly divided into: sham, spinal nerve ligation (SNL group, pain model), SNL + 100 mg CUR/kg BW (CUR group), and SNL + 50 mg CMO/kg BW (CMO group) for 4 weeks. Fecal samples were collected for microbiota composition analysis using 16S rRNA gene sequencing. The mRNA expression level of tight junction proteins (Claudin-1, Occludin) and neuroinflammation (NF-κB) in the colon, amygdala, and spinal cord using qRT-PCR. Data were analyzed statistically. RESULTS: Using a beta-diversity weighted UniFrac distance metric, the microbiome profile of the CMO-treated group was significantly different than other groups (P < 0.05). Regarding alpha-diversity, while most groups did not differ with respect to richness or evenness the CMO group improved microbiome evenness compared to the SNL group (P = 0.016). The relative abundance of several microbiome amplicon sequence variants (ASV) changed with different treatments. The SNL group showed a depletion in Rothia nasimurium compared to the sham group (P < 0.01). In contrast, Streptococcus and Clostridia ASVs (f_Oscillospiraceae; g_UCG−005) were enriched in the SNL group (P < 0.01). CUR or CMO treatments induced changes in multiple species compared to SNL. CUR and CMO reversed the enrichment effect of SNL on Clostridia ASV (P < 0.01). Compared to the sham group, the SNL group exhibited increased Claudin-1 mRNA expression levels in the amygdala. Relative to the SNL group, both CUR and CMO groups suppressed the mRNA gene expression of Claudin-1 (spinal cord, amygdala), Occludin (spinal cord, colon), and NF-κB (amygdala) in SNL-operated animals. CONCLUSIONS: This study suggests CUR and CMO administration modifies multiple species of gut microbiome in an NP model. These effects may be associated with a reduction in SNL-induced intestinal permeability and neuroinflammation. FUNDING SOURCES: Texas Tech University Health Sciences Center, Lubbock, TX.