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姜黄素通过改变粪便微生物群预防 AOM/DSS 小鼠结直肠癌的发生。

Alteration of fecal microbiota by fucoxanthin results in prevention of colorectal cancer in AOM/DSS mice.

机构信息

School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.

Advanced Research Promotion Center, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.

出版信息

Carcinogenesis. 2021 Feb 25;42(2):210-219. doi: 10.1093/carcin/bgaa100.

Abstract

Fucoxanthin (Fx), a marine carotenoid found in edible brown algae, is well known for having anticancer properties. The gut microbiota has been demonstrated as a hallmark for colorectal cancer progression in both humans and rodents. However, it remains unclear whether the gut microbiota is associated with the anticancer effect of Fx. We investigated the chemopreventive potency of Fx and its effect on gut microbiota in a mouse model of inflammation-associated colorectal cancer (by azoxymethane/dextran sulfate sodium treatment). Fx administration (30 mg/kg bw) during a 14 week period significantly inhibited the multiplicity of colorectal adenocarcinoma in mice. The number of apoptosis-like cleaved caspase-3high cells increased significantly in both colonic adenocarcinoma and mucosal crypts. Fx administration significantly suppressed Bacteroidlales (f_uc; g_uc) (0.3-fold) and Rikenellaceae (g_uc) (0.6-fold) and increased Lachnospiraceae (g_uc) (2.2-fold), compared with those of control mice. Oral administration of a fecal suspension obtained from Fx-treated mice, aimed to enhance Lachnospiraceae, suppress the number of colorectal adenocarcinomas in azoxymethane/dextran sulfate sodium-treated mice with a successful increase in Lachnospiraceae in the gut. Our findings suggested that an alteration in gut microbiota by dietary Fx might be an essential factor in the cancer chemopreventive effect of Fx in azoxymethane/dextran sulfate sodium-treated mice.

摘要

岩藻黄质(Fx)是一种存在于可食用褐藻中的海洋类胡萝卜素,具有抗癌特性。肠道微生物群已被证明是人类和啮齿动物结直肠癌进展的标志。然而,肠道微生物群是否与 Fx 的抗癌作用有关仍不清楚。我们在炎症相关结直肠癌的小鼠模型(通过氧化偶氮甲烷/葡聚糖硫酸钠处理)中研究了 Fx 的化学预防效力及其对肠道微生物群的影响。在 14 周的时间内,Fx 给药(30mg/kg bw)可显著抑制小鼠结直肠腺癌的多发性。在结肠腺癌和黏膜隐窝中,凋亡样裂解 caspase-3 高细胞的数量均显著增加。与对照组相比,Fx 给药可显著抑制拟杆菌目(f_uc;g_uc)(0.3 倍)和真杆菌科(g_uc)(0.6 倍),并增加厚壁菌门(g_uc)(2.2 倍)。来自 Fx 处理小鼠的粪便混悬液的口服给药旨在增强lachnospiraceae,抑制氧化偶氮甲烷/葡聚糖硫酸钠处理小鼠中的结直肠腺癌数量,成功地增加了肠道中的lachnospiraceae。我们的研究结果表明,膳食 Fx 引起的肠道微生物群的改变可能是 Fx 在氧化偶氮甲烷/葡聚糖硫酸钠处理小鼠中发挥癌症化学预防作用的一个重要因素。

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