Yogurt Prevents Colitis-Associated Colorectal Cancer in Mice.
Yogurt Prevents Colitis-Associated Colorectal Cancer in Mice.
复制标题
DOI：
10.1002/mnfr.202300444
复制
发表时间：
2023-10
影响因子：
5.2
通讯作者：
Xiaojing Li;Yongheng Yan;Xinru Du;Hao Zhang;Haitao Li;Wei Chen
中科院分区：
文献类型：
--
作者：
Xiaojing Li;Yongheng Yan;Xinru Du;Hao Zhang;Haitao Li;Wei Chen
SCOPE流行病学研究表明，酸奶摄入量与结直肠癌（CRC）之间呈负相关，但是否存在因果关系尚未得到验证。本研究旨在探讨酸奶对小鼠结肠炎相关结直肠癌（CAC）的影响和可能的机制。方法和结果实验性CAC由氧化偶氮甲烷（AOM，10 mg kg-1，腹膜内注射）诱导，随后进行三个周期的葡聚糖硫酸钠（DSS，3%）处理。通过在饮用水中添加 DSS (3%) 5 天来诱发结肠炎。分离原代小鼠巨噬细胞用于机制研究。数据清楚地表明，酸奶（15 g kg-1 体重）可显着降低小鼠结肠肿瘤的复数性达 38.83%。酸奶可以保护小鼠免受依赖于乳酸受体 GPR81 的结肠炎的影响。 Gpr81 的缺乏会加剧小鼠的结肠炎和 CAC。进一步的研究表明，GPR81 对于肠道屏障功能可能是可有可无的，但对于结肠粘膜修复至关重要。酸奶中的 d-乳酸可以激活 GPR81 抑制促炎巨噬细胞极化，从而促进结肠损伤后炎症消退，从而抑制 CAC 进展。结论 酸奶可以有效预防小鼠结肠炎相关的结直肠肿瘤发生，这项研究为慢性炎症性肠病患者补充酸奶提供了理论依据。
SCOPE Epidemiological studies indicate an inverse correlation between yogurt consumption and colorectal cancer (CRC), but whether there is a cause-and-effect relationship has not yet been validated. This study aims to investigate the effects and possible mechanisms of yogurt on colitis-associated colorectal cancer (CAC) in mice. METHODS AND RESULTS Experimental CAC is induced by azoxymethane (AOM, 10 mg kg-1 , ip) followed by three cycles of dextran sulfate sodium (DSS, 3%) treatment. Colitis is induced by adding DSS (3%) in drinking water for 5 days. Primary mouse macrophages are isolated for mechanistic studies. Data clearly show that yogurt (15 g kg-1 body weight) significantly reduces the multiplicity of colonic neoplasms by 38.83% in mice. Yogurt protects mice from colitis dependent on lactate receptor GPR81. The deficiency of Gpr81 exacerbates colitis and CAC in mice. Further investigation reveals that GPR81 may be dispensable for gut barrier function but essential for colonic mucosal repair. d-lactate in yogurt can activate GPR81 to suppress proinflammatory macrophage polarization, thereby facilitating inflammatory resolution after colonic injury and consequently suppressing CAC progression. CONCLUSION Yogurt effectively protects against colitis-associated colorectal tumorigenesis in mice, and this study provides a rationale for introducing yogurt supplementation to patients with chronic inflammatory bowel diseases.