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Clostridium butyricum modulates gut microbiota and reduces colitis associated colon cancer in mice.
International Immunopharmacology ( IF 5.6 ) Pub Date : 2020-08-06 , DOI: 10.1016/j.intimp.2020.106862
Miao Liu 1 , Wenjie Xie 2 , Xinyue Wan 1 , Tao Deng 1
Affiliation  

We investigate the effects of Clostridium butyricum(CB) on gut microbiota and colitis associated colon cancer(CAC) in mice.6–8 weeks old C57BL/6 mice were randomly divided into control, azoxymethane (AOM) + dextran sodium sulphate (DSS) and AOM + DSS + CB groups. Mice in the latter two groups received an intraperitoneal injection of AOM (12.5 mg/kg), followed by three cycles of DSS diluted in water (2.5% w/v). Mice in treatment group received CB (2 × 108 CFU in 200 ul normal saline) by gavage administration three times one week. Microbiota composition was assessed by 16S rRNA high-throughput sequencing. Colon samples were collected to examine severity of colitis and tumorigenesis. Cytokines including TNF-a, IL-6 and Cyclo-oxygenase-2 (COX-2) were detected by RT-qPCR. Expression of Bcl-2, Bax and the state of components of NF-κB signaling pathway were detected by western blot. The results revealed that CB regulated structure of intestinal flora and changed the microbial composition; decreased Firmicutes/ Bacteroidetes ratio in phylum level and increased the relative abundance of probiotics; decreased colitis, decreased incidence and size of colorectal cancer(CRC) and increased apoptosis of tumor cells; decreased cytokines including TNF-a and IL-6; decreased level of COX-2; decreased phosphorylation of NF-κB; decreased level of Bcl-2 and increased expression of Bax. In conclusion, CB could regulate structure and composition of gut microbiota and reduces colitis associated colon cancer in mice, the mechanism may be inhibiting NF-κB pathway and promoting apoptosis.



中文翻译:

丁酸梭菌可调节肠道菌群并减少小鼠结肠炎相关的结肠癌。

我们研究了丁酸梭菌(CB)对小鼠肠道菌群和结肠炎相关结肠癌(CAC)的影响。6–8周龄的C57BL / 6小鼠随机分为对照组,乙氧基甲烷(AOM)+葡聚糖硫酸钠(DSS)和AOM + DSS + CB组。后两组的小鼠接受腹膜内注射AOM(12.5 mg / kg),然后进行三个周期的DSS用水稀释(2.5%w / v)。治疗组小鼠接受CB(2×10 8每周三次通过管饲法在200 ul生理盐水中加入CFU。通过16S rRNA高通量测序评估微生物群组成。收集结肠样品以检查结肠炎和肿瘤发生的严重性。通过RT-qPCR检测到包括TNF-α,IL-6和环氧合酶-2(COX-2)在内的细胞因子。Western blot检测Bcl-2,Bax的表达及NF-κB信号通路的成分状态。结果表明,CB调节肠道菌群结构并改变了微生物组成。门生水平的硬毛/拟杆菌比率降低,益生菌的相对丰度增加;结肠炎减少,结直肠癌(CRC)的发生率和大小降低,肿瘤细胞凋亡增加;细胞因子减少,包括TNF-α和IL-6;COX-2水平降低;NF-κB的磷酸化降低;Bcl-2水平降低和Bax表达增加。总之,CB可以调节小鼠肠道菌群的结构和组成,减少结肠炎相关的结肠癌,其机制可能是抑制NF-κB通路并促进细胞凋亡。

更新日期:2020-08-06
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