Lactobacillus casei JY300-8 generated by 12C6+ beams mutagenesis inhibits tumor progression by modulating the gut microbiota in mice

Abstract

• A new mutant strain L. casei JY300-8 with excellent probiotic performance was generated by heavy ion beams irradiation induced-mutagenesis. • Probiotics JY300-8 was used for treat colon cancer and have a remarkable therapeutic effect in colon cancer mice. • JY300-8 was of better therapeutic effects, low treatment cost and less side effects compared to first-line therapy drug for cancer (DFUR) at an early state of colon cancer in mice. • JY300-8 significantly inhibited tumor progression by activating apoptosis of colon cells and regulating the gut microbiota in colon cancer mice. Probiotics, as novel functional foods via microbiota-modulation to enhance host health and inhibit tumor carcinogenesis, have been attracted considerable interests. L. casei JY, as a potential probiotic, was irradiated by 12 C 6+ beams and a new mutant strain JY300-8 was generated through three round selections of transit tolerance in the upper human gastrointestinal tract, adhesion ability to Caco-2 cells and inhibitory pathogenic microorganisms, respectively. Interestingly, JY300-8 presented excellent properties, including the strongest adhesion ability (86.81%) to Caco-2 cells to our knowledge and more excellent antimicrobial properties, which was used for the potential candidate probiotic. Additionally, JY300-8 could significantly inhibit the proliferation of Caco-2, HT29 and HCT116 cells in vitro, respectively. Furthermore, there were better therapeutic effects at an early stage in colon cancer mice, which included the similar survival rates (90%) and stronger inhibitory effect on tumor (83.48%), lower treatment cost and less side effects in comparison to the therapy drug (DFUR) for colon cancer (65.65%), which was attributed to promoting the apoptosis of colon cells and enhancing antitumor response via modulation cancer-induced gut microbiota dysbiosis by oral administration of JY300-8. Therefore, JY300-8 has great potential for bio-prophylactic and bio-therapeutic functional food in colon carcinogenesis. This work provided a promising approach that could improve human health, reduce greatly cancer incidence and mitigate cancer progression via modulation gut microbiota by excellent probiotics intervention.