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Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice.
Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2020-03-14 , DOI: 10.1007/s10565-020-09518-4
Ximei Ma 1 , Zhuha Zhou 1 , Xujun Zhang 2 , Mengjing Fan 3 , Yiyang Hong 3 , Ye Feng 4 , Qinghua Dong 3, 5 , Hongyan Diao 2 , Guanyu Wang 1
Affiliation  

Colorectal cancer (CRC) liver metastasis (CLM) is the leading death cause of CRC patients, but there is no satisfied approach to treat CLM. Gut microbiota plays a pivotal role in CRC initiation and development. Targeting dysbiosis of the gut microbiota might open up new opportunities for CLM treatment. Here, we investigated the efficacy of sodium butyrate (NaB), a major product of gut microbial fermentation, in modulating gut microbiota in CLM mice. NaB supplement decreased mouse colon cancer CT26 cell liver metastasis in intrasplenic tumor injection model of BALB/c mice. Using 16S rRNA gene sequencing, we found altered microbiota composition in CLM mice, characterized by increases of Firmicutes and Proteobacteria. NaB beneficially changed dysbiosis in CLM mice. Functional analysis of the KEGG pathways showed that NaB changed pathways related to immune system diseases and primary immunodeficiency in CLM mice. In addition, NaB decreased T regulatory cells and increased natural killer T cells and T helper 17 cells, accordingly decreased IL-10 and increased IL-17 secretion in CLM mice liver. In conclusion, NaB beneficially modulated gut microbiota and improved host immune response in CLM mice. These findings demonstrate the therapeutic potential of NaB in CLM treatment.



中文翻译:

丁酸钠调节结肠直肠癌肝转移小鼠的肠道微生物群和免疫反应。

结直肠癌(CRC)肝转移(CLM)是结直肠癌患者的首要死因,但目前尚无满意的治疗方法。肠道微生物群在 CRC 的发生和发展中起着关键作用。针对肠道微生物群的生态失调可能为 CLM 治疗开辟新的机会。在这里,我们研究了肠道微生物发酵的主要产物丁酸钠 (NaB) 在调节 CLM 小鼠肠道微生物群中的功效。在 BALB/c 小鼠的脾内肿瘤注射模型中,NaB 补充剂减少了小鼠结肠癌 CT26 细胞肝转移。使用 16S rRNA 基因测序,我们发现 CLM 小鼠的微生物群组成发生了改变,其特征是厚壁菌门和变形菌门的增加。NaB 有益地改变了 CLM 小鼠的生态失调。KEGG 通路的功能分析表明,NaB 改变了 CLM 小鼠与免疫系统疾病和原发性免疫缺陷相关的通路。此外,NaB 减少 T 调节细胞并增加自然杀伤 T 细胞和 T 辅助 17 细胞,相应地减少 CLM 小鼠肝脏中的 IL-10 和增加 IL-17 分泌。总之,NaB 有益地调节了 CLM 小鼠的肠道微生物群并改善了宿主免疫反应。这些发现证明了 NaB 在 CLM 治疗中的治疗潜力。NaB 有益地调节了 CLM 小鼠的肠道微生物群并改善了宿主免疫反应。这些发现证明了 NaB 在 CLM 治疗中的治疗潜力。NaB 有益地调节了 CLM 小鼠的肠道微生物群并改善了宿主免疫反应。这些发现证明了 NaB 在 CLM 治疗中的治疗潜力。

更新日期:2020-03-14
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