Resveratrol suppresses microglial activation and promotes functional recovery of traumatic spinal cord via improving intestinal microbiota

Abstract

Spinal cord injury (SCI) can change the intestinal microbiota pattern and corresponding metabolites, which in turn affect the prognosis of SCI. Among many metabolites, short-chain fatty acids (SCFAs) are critical for neurological recovery after SCI. Recent research has shown that resveratrol exerts anti-inflammatory properties. But it is unknown if the anti-inflammatory properties of resveratrol are associated with intestinal microbiota and metabolites. We thus investigate the alteration in gut microbiota and the consequent change of SCFAs following resveratrol treatment. The SCI mouse models with retention of gut microbiota (donor) and depletion of gut microbiota (recipient) were established. Fecal microbiota transplantation from donors to recipients was performed with intragastrical administration. Spinal cord tissues of mice were examined by H&E, Nissl, and immunofluorescence stainings. The expressions of the inflammatory profile were examined by qPCR and cytometric bead array. Fecal samples of mice were collected and analyzed with 16S rRNA sequencing. The results showed that resveratrol inhibited the microglial activation and promoted the functional recovery of SCI. The analysis of intestinal microbiota and metabolites indicated that SCI caused dysbiosis and the decrease in butyrate, while resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate. Both fecal supernatants from resveratrol-treated donors and butyrate suppressed the expression of pro-inflammatory genes in BV2 microglia. Our result demonstrated that fecal microbiota transplantation from resveratrol-treated donors had beneficial effects on the functional recovery of SCI. One mechanism of resveratrol effects was to restore the disrupted gut microbiota and butyrate.

Keywords: Fecal microbiota transplantation; Fecal supernatant; Microbiota; Resveratrol; SCFAs; Spinal cord injury; ampicillin (PubChem CID: 6249); butyric acid (PubChem CID: 264); isobutyric acid (PubChem CID: 6590); lipopolysaccharide (PubChem CID: 11970143); metronidazole (PubChem CID: 4173); neomycin (PubChem CID: 8378); resveratrol (PubChem CID: 445154); sodium butyrate (PubChem CID: 5222465).