Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner.
Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner.
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褪黑素以微生物群依赖性方式减轻恶唑酮诱发的结肠炎
DOI：
10.3389/fimmu.2021.783806
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发表时间：
2021
影响因子：
7.3
通讯作者：
Li YQ
中科院分区：
文献类型：
--
作者：
Zhao ZX;Yuan X;Cui YY;Liu J;Shen J;Jin BY;Feng BC;Zhai YJ;Zheng MQ;Kou GJ;Zhou RC;Li LX;Zuo XL;Li SY;Li YQ
活动期溃疡性结肠炎（UC）患者的血液和肠组织中2型细胞因子水平升高;这种现象表明2型免疫应答参与UC进展。褪黑激素在葡聚糖硫酸钠（DSS）和2，4，6-三硝基苯磺酸（TNBS）结肠炎模型中的有益作用已经被说明，但其在恶唑酮（Oxa）诱导的结肠炎模型（由2型免疫应答驱动）中的作用仍然相对未知。我们研究了褪黑素浓度与UC严重程度之间的关系，揭示了显着的负相关。随后，我们研究了褪黑素在Oxa诱导的结肠炎小鼠中的作用及其潜在的机制。褪黑激素的管理显着抵消体重减轻，结肠缩短，和嗜中性粒细胞浸润Oxa诱导的结肠炎小鼠。褪黑激素治疗通过抑制2型免疫应答减轻Oxa诱导的结肠炎。此外，褪黑激素通过增强结肠炎小鼠中ZO-1和occludin的表达来减弱肠通透性。有趣的是，当小鼠共同饲养时，褪黑激素的保护作用被消除，这表明褪黑激素对肠道微生物群的调节在缓解Oxa诱导的结肠炎中至关重要。随后，进行16 S rRNA测序以探索微生物群组成。褪黑激素治疗导致肠道微生物群在操作分类单位（OTU）水平上的丰富性和多样性降低。褪黑激素还提高了双歧杆菌（一种众所周知的益生菌）的丰度，并降低了几种有害细菌属的比例，如脱硫弧菌、消化球菌科和毛螺菌科。采用粪便微生物群移植（FMT）的方法，探讨微生物群在Oxa诱导的结肠炎中褪黑素功能的作用。从褪黑激素处理的小鼠中移植微生物群减轻了Oxa诱导的结肠炎，表明微生物群参与褪黑激素缓解Oxa诱导的结肠炎。我们的研究结果表明，褪黑激素以微生物群依赖性方式改善Oxa诱导的结肠炎，表明褪黑激素在治疗2型免疫相关UC中的治疗潜力。
Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.
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影响因子：
7.3
作者：
Ghareghani M;Reiter RJ;Zibara K;Farhadi N
通讯作者：
Farhadi N
褪黑激素介导的 MT2 通过 PI3K/AKT/Nrf2/SIRT1/RORα/NF-κB 信号通路减轻右旋糖酐硫酸钠诱导的结肠炎
影响因子：
5.6
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影响因子：
5.6
作者：
Cui H;Cai Y;Wang L;Jia B;Li J;Zhao S;Chu X;Lin J;Zhang X;Bian Y;Zhuang P
通讯作者：
Zhuang P
影响因子：
4.6
作者：
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通讯作者：
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影响因子：
5
作者：
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通讯作者：
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