Abstract
Background
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.
Methods
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.
Results
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).
Conclusions
JMR-01 LP + IP adjuvant 12C6+ irradiation could mitigate cancer progression by modulating innate immunity as well as intestinal flora.
Ethics statement
All institutional and national guidelines for the care and use of laboratory animals were followed.
Author contributions
All authors contributed to the study conception and design. Jin Bai, Shuyang Wang, and Guoqing Xiao designed the research study. Jin Bai, Xisi Sun, and Junkai Wang performed the experiments. Jin Bai wrote the manuscript. Jin Bai, Shuyang Wang, Fuqiang Xu, and Miaoyin Dong revised the paper, and all authors approved the final manuscript.
Disclosure statement
The authors declare no competing interests.
Additional information
Funding
Notes on contributors
Jin Bai
Jin Bai is a master student in the Institute of Modern Physics, Chinese Academy of Sciences.
Shuyang Wang
Shuyang Wang is a professor and PhD supervisor in the Institute of Modern Physics, Chinese Academy of Sciences.
Fuqiang Xu
Fuqiang Xu is a PhD student in the Institute of Modern Physics, Chinese Academy of Sciences.
Miaoyin Dong
Miaoyin Dong is a distinguished research assistant in the Institute of Modern Physics, Chinese Academy of Sciences.
Junkai Wang
Junkai Wang is a research assistant in the Institute of Modern Physics, Chinese Academy of Sciences.
Xisi Sun
Xisi Sun is a PhD student in the Institute of Modern Physics, Chinese Academy of Sciences.
Guoqing Xiao
Guoqing Xiao is a professor and PhD supervisor in the Institute of Modern Physics, Chinese Academy of Sciences.