Efficacy Evaluation of Selenium-enriched Akkermansia muciniphila in the Treatment of Colon Tumor Mice.

Abstract

Selenium (Se)-enriched probiotics possess a variety of beneficial properties and are widely used in specialty foods and biomedical applications. Akkermansia muciniphila (AM) is being considered a promising candidate for the "next generation probiotics (NGPs)," which play an essential role in the field of tumor therapy. However, there are no studies on the efficacy of Se-enriched A. muciniphila (Se-AM) in the field of tumor therapy. The present study utilized inorganic Se bio-enrichment for the preparation of Se-AM. To evaluate the killing effect of Se-AM on CT26 cells, the actual efficacy and safety of Se-AM were investigated in a mouse model of colon cancer. The results showed that the Se-AM-cell lysate was able to significantly kill CT26 cells, but this killing effect was progressively weakened with decreasing concentrations of Se-AM-cell lysate. The results of animal experiments showed that Se-AM was able to safely and effectively curb the disease course of mice with colon tumors, reduce the tumor volume, lower the levels of IL-1β and IL-6, and increase the levels of TNF-α in the colon of mice. Furthermore, treatment with Se-AM in mice led to a restoration of gut microbiota diversity, reaching levels similar to those observed in healthy controls. This restoration was accompanied by a significant enrichment of beneficial genera, such as Turicibacter, Butyricimonas, Prevotella, and Akkermansia. In summary, Se-AM prepared in this study was able to produce effective killing of CT26 cells directly and played a substantial therapeutic role in a mouse model of colon tumors constructed from CT26 cells. Se-AM had no adverse effect on the heart, liver, spleen, lungs, and kidney of mice and demonstrated a high level of safety. Meanwhile, Se-AM significantly raised the level of the Shannon index and the ratio of Firmicutes to Bacteroidetes of the gut microbiota in mice, indicating its ability to regulate the homeostasis of the microbiota. These results imply that Se-AM has great application value in the field of colon cancer treatment.