AUTHOR=Yun Bohyun , Ryu Sangdon , Kang Minkyoung , Lee Juyeon , Yoo Jiseon , Kim Younghoon , Oh Sangnam 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.819328

DOI=10.3389/fcimb.2021.819328

ISSN=2235-2988

ABSTRACT=<p>In this study, we investigated the relation of probiotic activity of <italic>Lacticaseibacillus rhamnosus</italic> strain GG (LGG) and expression of microRNA to immune response and longevity in <italic>Caenorhabditis elegans</italic> host model. First, we evaluated the survival rate of <italic>C. elegans</italic> due to LGG exposure and bacterial colonization in the intestine. Next, the expression of mRNA and miRNA was analyzed in <italic>C. elegans</italic> exposure to LGG for 24 h using microarray. After exposure to LGG to <italic>C. elegans</italic>, colonized LGG was observed in the intestines of <italic>C. elegans</italic> and induced to extend lifespan. Moreover, persistent LGG in the intestine significantly enhanced the resistance of <italic>C. elegans</italic> exposed to both pathogenic bacteria and prolonged the lifespan of <italic>C. elegans</italic>. 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 <italic>C. elegans</italic>, 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 <italic>miR-34</italic> and immune-related pathways increased by exposure to LGG, the lifespan of <italic>C. elegans</italic> increased. However, in the <italic>miR-34</italic> mutant <italic>C. elegans</italic>, the lifespan by LGG did not increase, so it was determined that <italic>miR-34</italic> 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 <italic>C. elegans</italic> enhances lifespan and resistance to food-borne pathogen infection by stimulating <italic>miR-34</italic> and indirectly promoting PMK-1 activity.</p>