P036 Faecalibacterium prausnitzii produces butyrate to maintain Th17/Treg balance and to ameliorate colorectal colitis by inhibiting histone deacetylase 1

Inflammatory bowel disease (IBD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose supernatant exerts an anti-inflammatory effect. However, the anti-inflammatory substances in F. prausnitzii supernatant and the mechanism in ameliorating colitis in IBD have not yet been fully investigated. Experimental colitis models were induced and evaluated by clinical examination and histopathology. Levels of cytokines and ratio of T cells were detected by enzyme-linked immunosorbent assay and flow cytometry analysis, respectively. F. prausnitzii supernatant was separated by microporous resins. After extraction, the substances in supernatant were identified by gas chromatography-mass spectrometer. T cell differentiation assay was conducted in vitro. Changes in signalling pathways were examined by western blot, immunohistochemistry and immunofluorescent staining. We found that the supernatant of F. prausnitzii could regulate T helper 17 cells (Th17)/ regulatory T cells (Treg) differentiation. Then, we identified that butyrate produced by F. prausnitzii that played the anti-inflammatory effects by inhibiting interleukin (IL)-6/signal transducer and activator of transcription three (STAT3)/IL-17 pathway and promoting forkhead box protein P3 (Foxp3). Finally, we demonstrated the target of butyrate was histone deacetylase 1 (HDAC1). It is butyrate, instead of other substances produced by F. prausnitzii, that maintains Th17/Treg balance and exerts significant anti-inflammatory effects in colorectal colitis rodents, by inhibiting HDAC1 to promote Foxp3 and block the IL-6/STAT3/IL-17 downstream pathway. F. prausnitzii could be an option for further investigation for IBD treatment. Targeting the butyrate-HDAC1-T cell axis offers an effective novel approach in the treatment of inflammatory disease.