L. reuteri JMR-01 adjuvant ¹²C⁶⁺ irradiation exerts anti-colon carcinoma effects by modulating the gut microbiota in mice

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.

Keywords:

• Probiotics
• heavy ion irradiation
• colon cancer
• Lactobacillus reuteri

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

This work was supported by ‘HONGGUANG’ Special Project of Chinese Academy of Sciences (KFJ-HGZX-001), the National Natural Science Foundation of China (No. 12075294), Key Research and Development Programs of Gansu Province (21YF5FA138) and the Local Cooperation Project of the Chinese Academy of Sciences (YD-2021-01).

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.