Protocatechuic Acid, a Gut Bacterial Metabolite of Black Raspberries, Inhibits Adenoma Development and Alters Gut Microbiome Profiles in Apc (Min/+) Mice.
Protocatechuic Acid, a Gut Bacterial Metabolite of Black Raspberries, Inhibits Adenoma Development and Alters Gut Microbiome Profiles in Apc (Min/+) Mice.
复制标题
原儿茶酸，黑树莓的肠道细菌代谢产物，抑制腺瘤发展并改变Apc（Min/+）小鼠的肠道微生物组谱。
DOI：
10.15430/jcp.2022.27.1.50
复制
发表时间：
2022-03-30
影响因子：
2.5
通讯作者：
Wang LS
中科院分区：
文献类型：
--
作者：
Dong A;Lin CW;Echeveste CE;Huang YW;Oshima K;Yearsley M;Chen X;Yu J;Wang LS
施用黑树莓（BRB）及其花青素代谢产物，包括原儿茶酸（PCA），已被证明通过改变先天免疫细胞运输，调节代谢和炎症途径等对结直肠癌发挥化学预防作用。先前的研究表明，肠道微生物组在结直肠癌的化学预防有效性中很重要。本研究旨在使用ApcMin/+小鼠模型评估PCA与BRB饮食管理预防结直肠癌的效力，并确定细菌谱如何响应PCA和BRB。向ApcMin/+小鼠施用补充有5%BRB、500 ppm PCA或1，000 ppm PCA的对照AIN-76 A饮食。完成饮食方案后，评估小肠和结肠腺瘤的发病率、息肉数量和息肉大小的变化。在小肠中通过饮食给予PCA和BRB以及在结肠中添加5% BRB的饮食，腺瘤的发展显著减少。在所有处理中，促炎细菌谱均被抗炎细菌取代，在5% BRB和500 ppm PCA补充饲料中效果最大，同时结肠粘膜中考克斯-2和前列腺素E2水平降低。我们进一步表明，500 ppm PCA，而不是1,000 ppm PCA，增加了原代培养的人类自然杀伤细胞中的IFN-γ和SMAD 4水平。这些结果表明，BRB和较低剂量的PCA都可以通过抑制腺瘤的生长和增殖并促进更有利的肠道微生物组条件而使结直肠癌患者受益。
Administration of black raspberries (BRBs) and their anthocyanin metabolites, including protocatechuic acid (PCA), has been demonstrated to exert chemopreventive effects against colorectal cancer through alteration of innate immune cell trafficking, modulation of metabolic and inflammatory pathways, etc. Previous research has shown that the gut microbiome is important in the effectiveness of chemoprevention of colorectal cancer. This study aimed to assess the potency of PCA versus BRB dietary administration for colorectal cancer prevention using an ApcMin/+ mouse model and determine how bacterial profiles change in response to PCA and BRBs. A control AIN-76A diet supplemented with 5% BRBs, 500 ppm PCA, or 1,000 ppm PCA was administered to ApcMin/+ mice. Changes in incidence, polyp number, and polyp size regarding adenomas of the small intestine and colon were assessed after completion of the diet regimen. There were significant decreases in adenoma development by dietary administration of PCA and BRBs in the small intestine and the 5% BRB-supplemented diet in the colon. Pro-inflammatory bacterial profiles were replaced with anti-inflammatory bacteria in all treatments, with the greatest effects in the 5% BRB and 500 ppm PCA-supplemented diets accompanied by decreased COX-2 and prostaglandin E2 levels in colonic mucosa. We further showed that 500 ppm PCA, but not 1,000 ppm PCA, increased IFN-γ and SMAD4 levels in primary cultured human natural killer cells. These results suggest that both BRBs and a lower dose PCA can benefit colorectal cancer patients by inhibiting the growth and proliferation of adenomas and promoting a more favorable gut microbiome condition.