Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms

Abstract

Caenorhabditis elegans, a non-parasitic nematode emerges as a relevant and powerful candidate as an in vivo model for microorganisms-microorganisms and microorganisms-host interactions studies. Experiments have demonstrated the probiotic potential of bacteria since they can provide to the worm a longer lifespan, an increased resistance to pathogens and to oxidative or heat stresses. Probiotics are used to prevent or treat microbiota dysbiosis and associated pathologies but the molecular mechanisms underlying their capacities are still unknown. Beyond safety and healthy aspects of probiotics, C. elegans represents a powerful way to design large-scale studies to explore transkingdom interactions and to solve questioning about the molecular aspect of these interactions. Future challenges and opportunities would be to validate C. elegans as an in vivo tool for high-throughput screening of microorganisms for their potential probiotic use on human health and to enlarge the panels of microorganisms studied as well as the human diseases investigated.

Keywords: Caenorhabditis elegans; immunity; lifespan; pathogens; probiotics; stress response.

Figure 1

Effects of bacterial probiotic strains on C. elegans lifespan. (A) Lifespan of C. elegans N2 fed with lactic acid bacteria compared to worms fed with E. coli OP50. The increase in the survival rate is represented for each strain as a percentage of the survival rate of C. elegans fed on E. coli OP50 (, , , , , , –91). (B) Negative effects of L. salivarius and L. reuteri on C. elegans lifespan. The decrease in the survival rate is represented for each strain as a percentage of the survival rate of C. elegans fed on E. coli OP50 (92). The decrease in the survival rate is represented for each strain as a percentage of the survival rate of C. elegans fed on E. coli OP50.

Figure 2

Effects of probiotics L. gasseri SBT2055 (86), L. rhamnosus CNCM I-3690 (11), B. longum (99), and B. subtilis NCIB3610 (114) on C. elegans during abiotic stress. During oxidative stress, the bacteria induce a response in the host via the p38 MAPK and DAF-2/DAF-16 pathways allowing the synthesis of antioxidant metabolites. In the case of thermal stress, a neural response induces the synthesis of heat-shock proteins to allow thermotolerance. In both cases, the result is an increase in the longevity of the host.

Figure 3

Molecular interactions and signaling pathways involved in C. elegans immune response. In the nematode, three highly conserved signaling pathways are the basis of the immune response protecting the animal from biological and abiotic aggression. These pathways are the p38 MAPK, the DAF-2/Insulin-like receptor and the JNK pathways. Interconnections and back-controls exist in these signal cascades and allow for fine control of the defense mechanisms put in place in the face of aggression. Transcriptomic analyses have revealed the absence of overlapping in the expression of genes regulated by these pathways.

Figure 4

(A) Strategy and workflow for screening, selecting, and studying probiotic microorganisms using an integrated process. A collection of microorganisms of interest must be tested by conventional in vitro methods to select strains that meet the eligibility criteria defined in the literature. These candidates are then characterized using the C. elegans model to describe their physiological and molecular characteristics to move on to the next steps. These consist of the establishment of preclinical models (i.e., rodents) and then clinical trials in humans before a possible marketing as a drug (or any other galenic form). (B) Manual C. elegans analysis workflow representing the numerous steps required by manual experiments. (C) Full automated C. elegans analysis workflow allowing a reduction in the number of steps, a reduction in the time required for the experimenter as well as biases inherent in handling errors.