L. reuteri FLRE5K1 inhibits the development and progression of hepatocellular carcinoma via activating the IFN-γ/CXCL10/CXCR3 pathway

Abstract Symbiotic bacteria participate in the formation of the structure and function of the tissues and organs in which they live, and play an essential role in maintaining the balance between health and disease. L. reuteri FLRE5K1 was isolated from the liver of healthy mice by our group and proved to be a probiotic with anti-melanoma activity in previous studies. The relationship between hepatic symbiotic probiotics and hepatocellular carcinoma (HCC) has not been reported yet. In the present study, L. reuteri FLRE5K1 was initially confirmed to successfully enter the liver after being administered by gavage, and the efficacy of probiotic feeding on HCC and its potential mechanism of inhibiting tumor progression were investigated by an orthotopic liver cancer model established. The results showed that L. reuteri FLRE5K1 significantly reduced the tumor formation rate and inhibited tumor growth. From the perspective of mechanism, activation of the IFN-γ/CXCL10/CXCR3 pathway as well as its positive feedback on the secretion of IFN-γ, induced the polarization of Th0 cell to Th1 cell and inhibited the differentiation of Treg cell, which played a key role in the inhibitory effect of L. reuteri FLRE5K1 on the development and progression of HCC.