L. reuteri JMR-01 辅助 12C6+ 辐照通过调节小鼠肠道微生物群落发挥抗结肠癌作用。
L. reuteri JMR-01 adjuvant 12C6+ irradiation exerts anti-colon carcinoma effects by modulating the gut microbiota in mice.
发表日期:2023 Feb 02
作者:
Jin Bai, Shuyang Wang, Fuqiang Xu, Miaoyin Dong, Junkai Wang, Xisi Sun, Guoqing Xiao
来源:
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
摘要:
类似乳酸菌的益生菌可以调节肠道微生物群落,已被视为改善结肠癌的有效策略。然而,其效果仍然是最大的挑战。我们研究了Lactobacillus reuteri JMR-01在CT-26同种小鼠模型中辅助12C6 +放射治疗的治疗效力。同时,肠道菌群和先天免疫力也被检查以阐明机制。活性和不活性益生菌JMR-01(LP + IP)对CT-26的抗增殖作用在体外当细胞与CFU比率为1:1时,在24小时达到最大值,为39.55%。这些活动也已在体内充分验证,受12C6 +放射治疗的肿瘤负荷的小鼠,结合活性和不活性益生菌JMR-01(IR + LP + IP)进行50天的治疗,获得最高生存率(71.4%)和完全缓解率(14.3%)。我们还证明了肠道微生物群落的显着波动,包括与肿瘤发生和发展有关的拟杆菌和产气荚膜梭菌的丰度下降,以及益生菌和双歧杆菌的丰度上升与小鼠的健康修复密切相关,这些小鼠用JMR-01 LP + IP辅助12C6 +放射治疗(IR + LP + IP)处理粪便时。同样,在IR + LP + IP组与肿瘤对照组相比,观察到一氧化还原酶活性降低和短链脂肪酸(SCFA)浓度增加,进一步证实了肠道微生物群落的变化。此外,我们发现与单一活体JMR-01(LP)和不活性JMR-01(IP)相比,LP + IP达到的脾细胞免疫刺激指数最强(2.47),腹膜巨噬细胞吞噬指数最强(3.68)。JMR-01 LP + IP辅助12C6 +放射治疗可以通过调节先天免疫系统和肠道菌群来缓解癌症进展。
Probiotics such as Lactobacillus could modulate the intestinal microbiota and have been considered as an effective strategy for ameliorating colon carcinoma. Nevertheless, its efficiency remains the biggest challenge.We investigated the therapeutic efficacy of Lactobacillus reuteri JMR-01 adjuvant 12C6+ irradiation on CT-26 syngeneic mouse models. Meanwhile, intestinal flora and innate immunity were examined to outline mechanisms.Anti-proliferation effect of live probiotic combined with inactivated probiotic JMR-01 (LP + IP) on CT-26 reached a maximum of 39.55% among other experiment groups at 24 h when the ratio of cell to CFU was 1:1 in vitro. These activities have been fully validated in vivo, tumor-bearing mice treated by 12C6+ irradiation combining with living and inactivated probiotics JMR-01 (IR + LP + IP) for 50-day held the highest survival rate (71.4%) and complete remission rate (14.3%). We also demonstrated significant fluctuation in gut microbiota, including the decreased abundance of Bacteroides fragilis and Clostridium perfringens related to tumorigenesis and development, and the increased abundance of Lactobacillus and Bifidobacterium closely associated with health restoration in fecal of mice treated with JMR-01 LP + IP adjuvant 12C6+ irradiation (IR + LP + IP). Similarly, the decreasing nitroreductase activities and increasing short chain fatty acids (SCFAs) concentrations were observed in IR + LP + IP group compared with tumor control group, which further confirmed the changes of gut microbiota. Additionally, we found that the strongest stimulation index of splenocyte (2.47) and the phagocytosis index peritoneal macrophage (3.68) were achieved by LP + IP compared with single live JMR-01 (LP) and inactivated JMR-01 (IP).JMR-01 LP + IP adjuvant 12C6+ irradiation could mitigate cancer progression by modulating innate immunity as well as intestinal flora.