Gut microbiota-derived queuine reprograms colon gene expression and alleviates colorectal cancer synergistically with Limosilactobacillus reuteri
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background Colorectal cancer (CRC) is a multifactorial disease of the colorectal epithelium that could be driven by gut microbiota dysregulation, while the molecular mechanisms of microbial metabolitesin regulating CRC remain unclear. Results We aim to investigate the biological functions of gut microbiota-derived queuine in the host and the underlying molecular mechanisms. Transcriptomic analysis of ten tissues from specific pathogen-free and germ-free mice revealed that queuine supplementation reprogrammed host gene expression, especially in the colon. Functionally, we found that queuine inhibited CRC in two cell lines (HCT116 and HT29), xenograft CRC mouse model, and CRC-derived organoids. Interestingly, we found that queuine supplementation in mice affected gut microbiota compositions, in which L. reuteri showed the most pronounced increase upon queuine treatment. Further experiments confirmed the effect of queuine on the activity of L. reuteri in vitro and in vivo . Moreover, L. reuteri enhanced the inhibitory effect from queuine on spontaneous colorectal cancer in mice. Mechanistically, both queuine and L. reuteri can suppress CRC through the regulation of Cdkn2a and Ctnnb1 . Conclusion s Our findings uncover the role and mechanism of gut microbiota-derived queuine in suppressing CRC, and we highlight the therapeutic potential of queuine and L. reuteri.
