小柯机器人

南京医科大学刘星吟研究团队发现，植物乳杆菌来源的吲哚-3乳酸通过CD8+ T细胞免疫的表观遗传调控改善结直肠癌(CRC)的发生。相关论文于2023年5月15日发表于国际顶尖学术期刊《细胞—代谢》杂志上。

本研究发现，植物乳杆菌L168及其代谢物吲哚-3-乳酸可改善肠道炎症、肿瘤生长和肠道生态失调。在机制上，他们发现吲哚-3-乳酸通过增强H3K27ac在IL12a增强子区域的结合，促进了CD8+ T细胞对肿瘤生长的免疫，从而加速了树突状细胞中IL12a的产生。此外，研究发现吲哚-3-乳酸通过改变肿瘤浸润性CD8+ T细胞的染色质可及性，进而增强其功能，从而转录抑制CD8+ T细胞胆固醇代谢相关的Saa3表达。

总之，他们的研究结果为益生菌介导的抗肿瘤免疫的表观遗传调控提供了新的见解，并表明L. plantarum L168和吲哚-3-乳酸有可能为结直肠癌患者制定治疗策略。

据介绍，先前的研究表明，乳杆菌种类在小鼠模型中起改善结CRC的作用。然而，潜在的机制在很大程度上仍然未知。

附：英文原文

Title: Lactobacillus plantarum-derived indole-3-lactic acid ameliorates colorectal tumorigenesis via epigenetic regulation of CD8+ T cell immunity

Author: Qingqing Zhang, Qing Zhao, Tao Li, Longya Lu, Fei Wang, Hong Zhang, Zhi Liu, Huihui Ma, Qihui Zhu, Jingjing Wang, Xuemei Zhang, Yang Pei, Qisha Liu, Yuyu Xu, Jinlong Qie, Xiaoting Luan, Zhibin Hu, Xingyin Liu

Issue&Volume: 2023-05-15

Abstract: Previous studies have shown that Lactobacillus species play a role in ameliorating colorectal cancer (CRC) in a mouse model. However,the underlying mechanisms remain largely unknown. Here, we found that administrationof a probiotic strain, Lactobacillus plantarum L168 and its metabolite, indole-3-lactic acid, ameliorated intestinal inflammation, tumorgrowth, and gut dysbiosis. Mechanistically, we indicated that indole-3-lactic acidaccelerated IL12a production in dendritic cells by enhancing H3K27ac binding at theenhancer regions of IL12a that contributed to priming CD8+ T cell immunity against tumor growth. Furthermore, indole-3-lactic acid was foundto transcriptionally inhibit Saa3 expression related to cholesterol metabolism ofCD8+ T cells through changing chromatin accessibility and subsequent enhancing functionof tumor-infiltrating CD8+ T cells. Together, our findings provide new insights into the epigenetic regulationof probiotics-mediated anti-tumor immunity and suggest the potential of L. plantarum L168 and indole-3-lactic acid to develop therapeutic strategies for patients with CRC.

DOI: 10.1016/j.cmet.2023.04.015

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00141-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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