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.