Probiotic Lacticaseibacillus rhamnosus GG Increased Longevity and Resistance Against Foodborne Pathogens in Caenorhabditis elegans by Regulating MicroRNA miR-34

Abstract

In this study, we investigated the relation of probiotic activity of <i>Lacticaseibacillus rhamnosus</i> strain GG (LGG) and expression of microRNA to immune response and longevity in <i>Caenorhabditis elegans</i> host model. First, we evaluated the survival rate of <i>C. elegans</i> due to LGG exposure and bacterial colonization in the intestine. Next, the expression of mRNA and miRNA was analyzed in <i>C. elegans</i> exposure to LGG for 24 h using microarray. After exposure to LGG to <i>C. elegans</i>, colonized LGG was observed in the intestines of <i>C. elegans</i> and induced to extend lifespan. Moreover, persistent LGG in the intestine significantly enhanced the resistance of <i>C. elegans</i> exposed to both pathogenic bacteria and prolonged the lifespan of <i>C. elegans</i>. Transcriptome analysis indicated that LGG affected the expression levels of genes related to the innate immune response and upregulated the abundance of genes in multiple pathways of <i>C. elegans</i>, including Wnt signaling, TGF-beta signaling and mitogen-activated protein kinase (MAPK) pathways. In addition, qRT-PCR analysis confirmed that the expression of antibacterial genes was increased by LGG. Moreover, as the expression of microRNA <i>miR-34</i> and immune-related pathways increased by exposure to LGG, the lifespan of <i>C. elegans</i> increased. However, in the <i>miR-34</i> mutant <i>C. elegans</i>, the lifespan by LGG did not increase, so it was determined that <i>miR-34</i> indirectly affects immune-related pathways. There was no significant difference in the expression of PMK-1 for LGG exposure in miR-34 mutants, suggesting that miR-34 may regulate PMK-1. In conclusion, we suggest that exposure of LGG to <i>C. elegans</i> enhances lifespan and resistance to food-borne pathogen infection by stimulating <i>miR-34</i> and indirectly promoting PMK-1 activity.