Faecalibacterium prausnitzii produces butyrate to decrease c-Myc-related metabolism and Th17 differentiation by inhibiting histone deacetylase 3
Faecalibacterium prausnitzii produces butyrate to decrease c-Myc-related metabolism and Th17 differentiation by inhibiting histone deacetylase 3
复制标题
普拉梭菌产生丁酸，通过抑制组蛋白脱乙酰酶 3 来减少 c-Myc 相关代谢和 Th17 分化
DOI：
10.1093/intimm/dxz022
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发表时间：
2019-08-01
影响因子：
4.4
通讯作者：
Yu, Chenggong
中科院分区：
文献类型：
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作者：
Zhang, Mingming;Zhou, Lixing;Yu, Chenggong
炎症性肠病(IBD)患者经常会发现其培养上清液具有抗炎作用的普氏杆菌(F.Prausnitzii)水平降低。然而，普氏华支睾吸虫上清液中的抗炎物质及其作用机制还没有得到充分的研究。在此，我们发现IBD患者肠道中的普氏锥虫和普氏福氏杆菌衍生的丁酸盐减少。补充普氏革兰氏杆菌上清液和丁酸盐可以改善动物模型中的结肠炎。丁酸盐，而不是普氏福氏杆菌产生的其他物质，通过抑制辅助性T细胞(Th17)的分化而发挥抗炎作用。普氏假丝酵母菌产生的丁酸丁酸酯的抗炎作用机制是通过抑制组蛋白脱乙酰酶3(HDAC3)促进乙酰化促进c-Myc的降解。综上所述，普氏假丝酵母菌通过抑制T细胞中HDAC3和c-Myc的相关代谢，产生丁酸盐，从而减少Th17的分化，减轻结肠炎。普氏疟原虫可能是治疗炎症性疾病的一种有效的降低Th17细胞水平的新途径。
Decreased levels of Faecalibacterium prausnitzii (F. prausnitzii), whose supernatant plays an anti-inflammatory effect, are frequently found in inflammatory bowel disease (IBD) patients. However, the anti-inflammatory products in F. prausnitzii supernatant and the mechanism have not been fully investigated. Here we found that F. prausnitzii and F. prausnitzii-derived butyrate were decreased in the intestines of IBD patients. Supplementation with F. prausnitzii supernatant and butyrate could ameliorate colitis in an animal model. Butyrate, but not other substances produced by F. prausnitzii, exerted an anti-inflammatory effect by inhibiting the differentiation of T helper 17 (Th17) cells. The mechanism underlying the anti-inflammatory effects of the butyrate produced by F. prausnitzii involved the enhancement of the acetylation-promoted degradation of c-Myc through histone deacetylase 3 (HDAC3) inhibition. In conclusion, F. prausnitzii produced butyrate to decrease Th17 differentiation and attenuate colitis through inhibiting HDAC3 and c-Myc-related metabolism in T cells. The use of F. prausnitzii may be an effective new approach to decrease the level of Th17 cells in the treatment of inflammatory diseases.