Probiotic Lactobacillus brevis CLB3 prevents azoxymethane/dextran sulfate sodium-induced colon carcinogenesis in mice by reducing amino acid transport and IL-17A levels and repressing the IL-6/AKT/p-STAT3 signaling pathway

Abstract

Abstract Amino acid intake plays a crucial role in the Warburg effect of cancer. Gut microbes can regulate intestinal amino acid metabolism. However, it is still unknown whether probiotic therapy can protect the host from intestinal tumor invasion by reducing amino acid intake. With in vitro methods, three acid-tolerant strains from fermented pickles were screened out. Using azoxymethane/dextran sulfate sodium-induced colon cancer models, we evaluated the therapeutic effects of Lactobacillus brevis CLB3, Lactobacillus plantarum XLP, and Lactobacillus johnsonii CM on model mice. Their functional mechanisms were further explained through anatomy section, quantitative reverse transcrip­tion polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical staining analyses as well as database mining and gut culturomics. The Lactobacillus brevis (L. brevis) CLB3 treatment significantly improved the clinical signs and symptoms of colon cancer, alleviated colon damage, and inhibited colon carcinogenesis in mice. In addition, this treatment significantly increased gut cultivable Lactobacillus abundance, inhibited the expression and translation levels of the tumor metabolism-related solute carrier (SLC) amino acid transporter including SLC7A5 and SLC7A11, lowered circulating interleukin-6 (IL-6) and interleukin-17A (IL-17A) levels, and improved the accumulation of tumor-infiltrating lymphocytes and cancer proliferation factors. These findings suggest that L. brevis CLB3 can reduce amino acid transport, inhibit mammalian target of rapamycin (mTOR) signaling and enhance intestinal anti-tumor immune responses, which provides a potential targeting amino acid transporter strategy for preventing colorectal cancer.