Elucidating the cell signaling pathways for epithelial restitution of a novel probiotic

Abstract

Probiotics are a group of beneficial bacteria that when consumed in adequate amounts confer a health benefit. Recently, our group showed that a novel probiotic, Lactococcus lactis sp cremoris (LLC) can elicit strong intestinal cytoprotection in murine experimental models of intestinal damage, and potently enhance restitution of a damaged gut epithelium. The objective of this study was to elucidate the mechanism whereby LLC promotes epithelial restitution. Our goal was to first identify which host pattern recognition receptor that could recognize LLC. We gavaged LLC or vehicle control to mice and assessed transcript enrichment in the colon after 4 hours by RNA‐seq. We detected the specific upregulation of TLR2. We next investigated whether a soluble factor from LLC was able to be detected by TLR2. To test this, we cultured epithelial monolayers with supernatant from an LLC overnight culture and detected elevated TLR2 expression. Furthermore, we detected potent activation of the NF‐kB pathway, and the Nrf2 signaling pathway in epithelial cells following contact by LLC supernatant. Importantly, no negative physiological influences, or cytotoxicity were detected in these cells. Functionally, we found that LLC supernatant accelerated the closure of scratch wound inflicted on an epithelial monolayer in a TLR2‐dpendant manner. These and other data were evidence for us to conclude that LLC mediates epithelial restitution through a TLR2‐dependent pathway. We also propose that cross‐talk between the NF‐kB and Nrf2 cell signaling pathways function in the beneficial effect of LLC on intestinal health and restitution following disease or injury.Support or Funding InformationThis work was supported by the NIDDK‐ R01DK098391This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.