Journal
INFLAMMATORY BOWEL DISEASES
Volume 24, Issue 9, Pages 1926-1940Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/ibd/izy182
Keywords
Faecalibacterium prausnitzii; inflammatory bowel disease; regulatory T cells; T helper 17 cells; butyrate; histone deacetylase
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Funding
- National Natural Science Foundation of China [81470819, 81602076]
- Natural Science Foundation from the Department of Science and Technology of Jiangsu Province [BK20160113]
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Background: Inflammatory bowel disease (IBD)-associated dysbiosis is characterized 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. Methods: 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 macroporous resins. After extraction, the substances in supernatant were identified by gas chromatography-mass spectrometer. T-cell differentiation assay was conducted in vitro. Changes in signaling pathways were examined by immunoblot, immunohistochemistry, and immunofluorescent staining. Results: We found that the supernatant of F. prausnitzii could regulate T helper 17 cell (Th17)/regulatory T cell (Treg) differentiation. Then, we identified butyrate produced by F. prausnitzii that played the anti-inflammatory effects by inhibiting interleukin (IL)-6/signal transducer and the activator of transcription 3 (STAT3)/IL-17 pathway and promoting forkhead box protein P3 (Foxp3). Finally, we demonstrated that the target of butyrate was histone deacetylase 1 (HDAC1). Conclusions: 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.
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