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Inflamm Bowel Dis. 2018 May 23. doi: 10.1093/ibd/izy182. [Epub ahead of print]

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

Author information

1
Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
2
Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.
3
School of Life Sciences, Fudan University, Shanghai, China.
4
Northwestern University Feinberg School of Medicine, Chicago, Illinois.
5
Department of Pharmacy, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
6
Department of Gastroenterology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
7
Department of Digestive Diseases of Huashan Hospital, Shanghai, China.
8
Key Laboratory, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

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.

PMID:
29796620
DOI:
10.1093/ibd/izy182

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