Melatonin controls microbiota in colitis by goblet cell differentiation and antimicrobial peptide production through Toll-like receptor 4 signalling
Melatonin controls microbiota in colitis by goblet cell differentiation and antimicrobial peptide production through Toll-like receptor 4 signalling
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DOI：
10.1038/s41598-020-59314-7
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发表时间：
2020-02-10
影响因子：
4.6
通讯作者：
Park, Young Sook
中科院分区：
文献类型：
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作者：
Kim, Seung Won;Kim, Soochan;Park, Young Sook
长期以来，微生物生态失调被认为与炎症性肠病（IBD）的发病机制有关。虽然支持褪黑激素抗结肠炎作用的证据已经积累，但褪黑激素如何影响微生物群尚不清楚。在本文中，我们研究了褪黑激素对结肠炎中微生物组的影响，并确定了Toll样受体（TLR）4信号传导参与这些影响。褪黑激素改善了葡聚糖硫酸钠（DSS）诱导的结肠炎，并在野生型（WT）小鼠中恢复了微生物生态失调，但在TLR 4敲除（KO）小鼠中没有。用褪黑激素给药观察到杯状细胞的诱导，这伴随着对Il 1b和Il 17 a的抑制以及褪黑激素受体和Reg 3 β（一种针对革兰氏阴性菌的抗菌肽（AMP））的诱导。在体外，褪黑激素治疗HT-29肠上皮细胞促进粘蛋白和伤口愈合，并抑制大肠杆菌的生长。在本文中，我们表明褪黑激素通过TLR 4信号传导抑制革兰氏阴性菌来显著增加杯状细胞、Reg 3 β和厚壁菌门与拟杆菌门的比率。我们的研究表明，通过TLR 4的细菌和细菌的调节，通过改变杯状细胞和AMP的传感器参与褪黑素的抗结肠炎作用。褪黑激素可用于IBD的治疗。
Microbial dysbiosis has long been postulated to be associated with the pathogenesis of inflammatory bowel disease (IBD). Although evidence supporting the anti-colitic effects of melatonin have been accumulating, it is not clear how melatonin affects the microbiota. Herein, we investigated the effects of melatonin on the microbiome in colitis and identified involvement of Toll-like receptor (TLR) 4 signalling in the effects. Melatonin improved dextran sulfate sodium (DSS)-induced colitis and reverted microbial dysbiosis in wild-type (WT) mice but not in TLR4 knockout (KO) mice. Induction of goblet cells was observed with melatonin administration, which was accompanied by suppression of Il1b and Il17a and induction of melatonin receptor and Reg3 beta, an antimicrobial peptide (AMP) against Gram-negative bacteria. In vitro, melatonin treatment of HT-29 intestinal epithelial cells promotes mucin and wound healing and inhibits growth of Escherichia coli. Herein, we showed that melatonin significantly increases goblet cells, Reg3 beta, and the ratio of Firmicutes to Bacteriodetes by suppressing Gram-negative bacteria through TLR4 signalling. Our study suggests that sensing of bacteria through TLR4 and regulation of bacteria through altered goblet cells and AMPs is involved in the anti-colitic effects of melatonin. Melatonin may have use in therapeutics for IBD.