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

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

doi:10.3389/fcimb.2021.819328

Abstract

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

Highlights

Lacticaseibacillus rhamnosus strain GG (LGG) is one of the most widely studied probiotic strains for dairy foods including yogurt and cheese, and is generally recognized as safe (GRAS) by the Food and Drug Administration (Groele et al, 2017)
Lifespan analyses were performed by monitoring the LGG-fed C. elegans, starting at the L4 larval stage, compared to the control C. elegans exposed to the nonpathogenic prey E. coli OP50 or probiotic strain LGG (Figure 1A)
We found no significant difference in the lifespan of C. elegans exposed to OP50 and LGG in C. elegans (Figure 1B)

Summary

Introduction

Lacticaseibacillus rhamnosus strain GG (LGG) is one of the most widely studied probiotic strains for dairy foods including yogurt and cheese, and is generally recognized as safe (GRAS) by the Food and Drug Administration (Groele et al, 2017). LGG, originally isolated from human feces by Gorbach and Goldin (Segers and Lebeer, 2014), is an ideal probiotic that is resistant to stomach acid and bile, so it can survive the gastrointestinal tract, has the ability to consistently implant human intestinal epithelial cells and colonize the gut, produces an antimicrobial substance, has a rapid growth rate, and has beneficial effects on health (Doron et al, 2005). Yan et al reported that the LGG-derived protein p40 prevents and treats colon epithelial cell damage and inflammation in a colitis model (Yan et al, 2011). Lin et al reported that LGG can protect against deoxynivalenolinduced bowel damage by regulating the intestinal microflora to promote the production of butyrate and thereby inhibit the IRE1a/XBP1 signaling pathway (Lin et al, 2020). LGG can reduce the risk of colon cancer by regulating the intestinal microflora and downregulating pro-inflammatory molecules (Gamallat et al, 2019)

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Results