Weissella koreensis regulates mitochondrial protective genes and innate immune genes to enhance anti-bacterial immunity

Abstract

Probiotics are widely recognized for their ability to promote gut health, modulate immunity, and reduce oxidative stress. As an emerging probiotic within the genus Weissella , Weissella koreensis (WK) exhibits promising immunomodulatory potential. Recent evidence highlights its potential as a functional probiotic in combating obesity. However, its specific role in host immune regulation and the underlying molecular mechanisms remain largely undefined. In this study, we demonstrate that, compared to the OP50-fed controls, WK significantly increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Staphylococcus aureus and Enterococcus faecalis by promoting intestinal bacterial clearance. Through genetic analysis in Caenorhabditis elegans , we find that WK promotes innate immunity via the transcription factor ATFS-1. We further show that WK activates the mitochondrial unfolded protein response (UPR mt ) and downstream innate immune effector genes through ATFS-1. In addition, WK decreases reactive oxygen species (ROS) levels and increases adenosine triphosphate (ATP) levels in C. elegans . Consistent with a potentially conserved host response, WK treatment in mice improved survival, reduced pulmonary bacterial burden, and increased the transcription of Atf5 and associated mitochondrial-protective genes. These findings advance our understanding of the immunomodulatory functions of Weissella koreensis and highlight its efficacy as a novel therapeutic strategy for immune intervention.