Pilin SpaC‐mediated epithelial adhesion is required for Lactobacillus rhamnosus GG‐induced probiotic effects (60.9)

Abstract

Lactobacillus rhamnosus GG (LGG) is a widely used probiotic, and the strain’s salutary effects on the intestine have been extensively documented. We have demonstrated this strain can modulate inflammatory signaling, as well as epithelial migration and proliferation via stimulation of Nox1 dependent reactive oxygen species. However, how this strain mediates these effects is largely unknown. Here, we report that LGG’s probiotic benefits are dependent on the SpaC pilin subunit. By comparing LGG to an isogenic mutant that lacks SpaC (LGGΩSpaC) in a variety of in vitro and in vivo assays, we establish that SpaC is necessary for LGG to adhere to gut mucosa, that SpaC contributes to LGG’s ability to induce the epithelial generation of ROS, and that SpaC plays a role in LGG’s capacity to stimulate the phosphorylation of ERK in enterocytes. In addition, we show that SpaC is required for LGG‐mediated stimulation of cell proliferation, and protection against radiologically‐inflicted intestinal injury. The identification of a critical surface protein required for LGG to mediate its probiotic influence furthers our understanding of the molecular basis for the symbiotic relationship between some commensal bacteria of the gut lumen and enterocytes. Further insights into this relationship are critical for the development of novel approaches to treat inflammatory bowel diseases and other intestinal disorders.Grant Funding Source: Supported by NIH RO1 AI 64462