Maggot extracts chemo-prevent inflammation and tumorigenesis accompanied by changes in the intestinal microbiome and metabolome in AOM/DSS-induced mice.

Maggot extracts chemo-prevent inflammation and tumorigenesis accompanied by changes in the intestinal microbiome and metabolome in AOM/DSS-induced mice.
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DOI:
10.3389/fmicb.2023.1143463
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发表时间:
2023
影响因子:
5.2
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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炎症反应和肠道微生物组在结肠炎相关癌(CAC)的进展中起关键作用。中药蛆因其临床应用和抗炎作用而广为人知。在本研究中,我们研究了蛆提取物(ME)在氮氧甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导的小鼠CAC前灌胃的预防作用。结果显示,与AOM/DSS组相比,ME在改善疾病活动指数评分和炎症表型方面具有优势。预用药后结肠息肉样肿瘤的数量和大小均减少。此外,我们发现ME可以逆转模型中紧密连接蛋白(occluden-1和occluden)的下调,同时抑制炎症因子(IL-1β和IL-6)的水平。此外,toll样受体4 (TLR4)介导细胞内核因子-κB (NF-κB)信号级联反应,包括诱导型一氧化氮合酶和环氧化酶-2,并在ME预给药后小鼠模型中表达降低。16s rRNA分析和粪便样本的非靶向代谢组学分析推断,ME可以理想地预防CAC小鼠肠道生态失调,并伴有代谢物组成的改变并与之相关。总的来说,在CAC的发生和发展中,ME预给药可能是一种化学预防候选药物。
Inflammatory responses and intestinal microbiome play a crucial role in the progression of colitis-associated carcinoma (CAC). The traditional Chinese medicine maggot has been widely known owing to its clinical application and anti-inflammatory function. In this study, we investigated the preventive effects of maggot extract (ME) by intragastric administration prior to azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CAC in mice. The results showed that ME had superior advantages in ameliorating disease activity index score and inflammatory phenotype, in comparison with the AOM/DSS group. The number and size of polypoid colonic tumors were decreased after pre-administration of ME. In addition, ME was found to reverse the downregulation of tight junction proteins (zonula occluden-1 and occluding) while suppressing the levels of inflammatory factors (IL-1β and IL-6) in models. Moreover, Toll-like receptor 4 (TLR4) mediated intracellular nuclear factor-κB (NF-κB)-containing signaling cascades, including inducible nitric oxide synthase and cyclooxygenase-2, and exhibited decreasing expression in the mice model after ME pre-administration. 16s rRNA analysis and untargeted-metabolomics profiling of fecal samples inferred that ME revealed ideal prevention of intestinal dysbiosis in CAC mice, accompanied by and correlated with alterations in the composition of metabolites. Overall, ME pre-administration might be a chemo-preventive candidate in the initiation and development of CAC.
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