Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1

• Published in: Inflammatory bowel diseases Vol. 24; no. 9; pp. 1926 - 1940
• Main Authors: Zhou, Lixing, Zhang, Mingming, Wang, Yuming, Dorfman, Robert Gregory, Liu, Hang, Yu, Ting, Chen, Xiaotian, Tang, Dehua, Xu, Lei, Yin, Yuyao, Pan, Yida, Zhou, Qian, Zhou, Yihua, Yu, Chenggong
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 16.08.2018
• Subjects: Animals; Butyrates - metabolism; Cell Differentiation; Colitis - chemically induced; Colitis - microbiology; Colon - microbiology; Disease Models, Animal; Dysbiosis - microbiology; Faecalibacterium prausnitzii - metabolism; Histone Deacetylase 1 - antagonists & inhibitors; Histone Deacetylase 1 - metabolism; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Sprague-Dawley; Rectum - microbiology; Signal Transduction; T-Lymphocytes, Regulatory - microbiology; Th17 Cells - microbiology; regulatory T cells; T helper 17 cells; butyrate; histone deacetylase; inflammatory bowel disease; Faecalibacterium prausnitzii
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1093/ibd/izy182

Abstract 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.